U.S. patent application number 15/383056 was filed with the patent office on 2017-10-12 for compositions comprising bile acid sequestrants for treating esophageal disorders.
This patent application is currently assigned to Ironwood Pharmaceuticals, Inc.. The applicant listed for this patent is Ironwood Pharmaceuticals, Inc.. Invention is credited to Mark G. CURRIE.
Application Number | 20170290767 15/383056 |
Document ID | / |
Family ID | 39277294 |
Filed Date | 2017-10-12 |
United States Patent
Application |
20170290767 |
Kind Code |
A1 |
CURRIE; Mark G. |
October 12, 2017 |
COMPOSITIONS COMPRISING BILE ACID SEQUESTRANTS FOR TREATING
ESOPHAGEAL DISORDERS
Abstract
Disclosed herein are novel compositions and methods for treating
or preventing upper GI tract disorders and protecting stratified
squamous epithelium against injury by a noxious substance. The
methods generally include administering to a patient in need
thereof a therapeutically effective amount of a pharmaceutical
composition comprising at least one bile acid sequestrant, alone or
in combination with at least one proton pump inhibitor, and
optionally one or more agent chosen from antacids, histamine
H.sub.2-receptor antagonists, .gamma.-aminobutyricacid-b (GABA-B)
agonists, prodrugs of GABA-B agonists, and protease inhibitors.
Inventors: |
CURRIE; Mark G.; (Boston,
MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Ironwood Pharmaceuticals, Inc. |
Cambridge |
MA |
US |
|
|
Assignee: |
Ironwood Pharmaceuticals,
Inc.
Cambridge
MA
|
Family ID: |
39277294 |
Appl. No.: |
15/383056 |
Filed: |
December 19, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14931215 |
Nov 3, 2015 |
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15383056 |
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12520748 |
Feb 18, 2010 |
9205094 |
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PCT/US2007/088624 |
Dec 21, 2007 |
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14931215 |
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60871499 |
Dec 22, 2006 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 9/0007 20130101;
A61K 31/444 20130101; A61K 31/575 20130101; A61K 31/4184 20130101;
A61K 31/4439 20130101; A61K 31/195 20130101; A61K 31/4439 20130101;
A61K 31/4164 20130101; A61K 31/785 20130101; A61K 33/08 20130101;
A61K 31/426 20130101; A61K 31/195 20130101; A61K 31/27 20130101;
A61K 31/27 20130101; A61K 31/4184 20130101; A61K 33/10 20130101;
A61K 31/444 20130101; A61P 1/04 20180101; A61K 9/0065 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 45/06 20130101;
A61K 31/341 20130101; A61K 2300/00 20130101; A61K 31/4164 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 2300/00 20130101; A61K 2300/00 20130101; A61K
2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 31/426 20130101; A61K 31/575 20130101; A61K 31/341 20130101;
A61K 33/10 20130101; A61K 31/785 20130101; C08F 226/02 20130101;
A61K 2300/00 20130101; A61K 33/08 20130101 |
International
Class: |
A61K 9/00 20060101
A61K009/00; A61K 33/10 20060101 A61K033/10; A61K 31/444 20060101
A61K031/444; A61K 33/08 20060101 A61K033/08; A61K 31/195 20060101
A61K031/195; A61K 31/4184 20060101 A61K031/4184 |
Claims
1-122. (canceled)
123. A sustained-release pharmaceutical dosage form for oral
administration to a subject in need thereof comprising an amount of
at least one bile acid sequestrant that is in a range from 0.1 g to
1.0 g, wherein: the at least one bile acid sequestrant is selected
from the group consisting of colesevelam, colesevelam
hydrochloride, and combinations thereof, and a gastric-retention
vehicle composition comprising one or more hydrogels; said dosage
form expands upon contact with gastric fluid; characterized in that
the dosage form is retained in a person's stomach for a period of
three hours or more following ingestion; and the percentage of bile
acid sequestrant is present in an amount from between 10% to about
75% of the total weight.
124. The sustained-release pharmaceutical dosage form for oral
administration according to claim 123, further comprising a
therapeutically effective amount of at least one proton pump
inhibitor in a range from 1 mg to 200 mg.
125. The sustained-release pharmaceutical dosage form for oral
administration of claim 124, wherein the at least one proton pump
inhibitor is selected from omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole, tenatoprazole, leminoprazole,
dontoprazole and ransoprazole.
126. The sustained-release pharmaceutical dosage form for oral
administration of claim 125, wherein the at least one proton pump
inhibitor is omeprazole.
127. A method for mitigating the presence of bile acid in the upper
gastrointestinal (GI) tract, comprising administering to a patient
a therapeutically effective amount of the sustained-release
pharmaceutical dosage form for oral administration according claim
123.
128. A method for mitigating the presence of bile acid in the upper
gastrointestinal (GI) tract, comprising administering to a patient
that has or is at risk of developing said disorder a
therapeutically effective amount of the sustained-release
pharmaceutical dosage form for oral administration according to
claim 124.
129. The method according to claim 128, further comprising:
simultaneously, separately, or sequentially administering to said
patient at least one proton pump inhibitor.
130. The method according to claim 129, further comprising:
simultaneously, separately, or sequentially administering to said
patient at least one proton pump inhibitor.
Description
BACKGROUND
[0001] The present application relates generally to combinations of
compounds and methods for treating upper gastrointestinal tract
disorders. More particularly, the present application relates to
the use of at least one bile acid sequestrant for treating
esophageal disorders.
[0002] The esophagus carries food, liquids, and saliva from the
mouth to the stomach by coordinated contractions of its muscular
lining. This process is automatic and people are usually not aware
of it. Many people have felt their esophagus when they swallow
something too large, try to eat too quickly, or drink very hot or
very cold liquids. They then feel the movement of the food or drink
down the esophagus into the stomach, which may be an uncomfortable
sensation.
[0003] The muscular layers of the esophagus are normally pinched
together at both the upper and lower ends by muscles called
sphincters. When a person swallows, the sphincters relax
automatically to allow food or drink to pass from the mouth into
the stomach. The muscles then close rapidly to prevent the
swallowed food or drink from leaking out of the stomach back into
the esophagus or into the mouth. These sphincters make it possible
to swallow while lying down or even upside-down. When people belch
to release swallowed air or gas from carbonated beverages, the
sphincters relax and small amounts of food or drink may come back
up briefly; this condition is called reflux. The esophagus quickly
squeezes the material back into the stomach. This amount of reflux
and the reaction to it by the esophagus are considered normal.
[0004] While most people are familiar with acid reflux--the
backflow of caustic stomach acids into the esophagus--bile reflux,
which occurs when bile--a digestive fluid produced in the
liver--flows upward (refluxes) from the small intestine into the
stomach and esophagus, is less well known. Bile reflux often
accompanies acid reflux, and together may lead to inflammation of
the esophageal lining and potentially increased risk of esophageal
cancer. See AJG (1999) 94(12):3649-3650. Bile reflux also affects
the stomach, where it causes further inflammation.
[0005] Unlike acid reflux, bile reflux usually can't be controlled
by changes in diet or lifestyle. Instead, bile reflux is most often
managed with certain medications or, in severe cases, with surgery.
Neither solution is uniformly effective, however, and some people
continue to experience bile reflux even after treatment.
[0006] Bile reflux can be difficult to distinguish from acid
reflux--the signs and symptoms are similar, and the two conditions
frequently occur at the same time. Unlike acid reflux, bile reflux
inflames the stomach, often causing a gnawing or burning pain in
the upper abdomen. Other signs and symptoms may include: frequent
heartburn, i.e., a burning sensation in the chest that sometimes
spreads to the throat along with a sour taste in the mouth; nausea;
vomiting bile; a cough; or hoarseness.
[0007] Bile and stomach acid reflux into the esophagus when the
lower esophageal sphincter (LES), malfunctions. The LES separates
the esophagus and stomach. Normally, it opens only to allow food to
pass into the stomach and then closes tightly. But if the valve
relaxes abnormally or weakens, stomach acid and bile can wash back
into the esophagus, causing heartburn and ongoing inflammation that
may lead to serious complications.
[0008] A sticky mucous coating protects the stomach from the
corrosive effects of stomach acid, but the esophagus lacks this
protection, which is why bile reflux and acid reflux can seriously
damage esophageal tissue. And although bile reflux can injure the
esophagus on its own--even when the pH of the reflux is neutral or
alkaline--the combination of bile and acid reflux seems to be
particularly harmful, increasing the risk of complications, such
as: Gastroesophageal reflux disease, or GERD; Barrett's esophagus;
esophageal cancer, and gastritis.
[0009] GERD is a generic term encompassing diseases with various
digestive symptoms such as pyrosis, acid regurgitation, obstructed
admiration, aphagia, pectoralgia, permeating feeling and the like
sensibility caused by reflux in the esophagus and stagnation of
gastric contents, duodenal juice, pancreatic juice and the like.
The term covers both of reflux esophagitis in which erosion and
ulcers are endoscopically observed, and esophageal
regurgitation-type non-ulcer dyspepsia (NUD) in which no
abnormality is endoscopically observed. GERD occurs when the LES
does not close properly and stomach contents leak back, or reflux,
into the esophagus.
[0010] A hiatal hernia may contribute to causing GERD and can
happen in people of any age. Other factors that may contribute to
GERD include, but are not limited to, alcohol use, overweight,
pregnancy, smoking, Zollinger-Ellison syndrome, hypercalcemia, and
scleroderma. Also, certain foods can be associated with reflux
events, including, citrus fruits, chocolate, drinks with caffeine,
fatty and fried foods, garlic and onions, mint flavorings, spicy
foods, and tomato-based foods, like spaghetti sauce, chili, and
pizza.
[0011] The inner mucosa of the esophagus is lined with
nonkeratinized stratified squamous epithelium arranged in
longitudinal folds. Damage to the lining of the esophagus causes
the normal squamous cells that line the esophagus to turn into a
type of cell not usually found in humans, called specialized
columnar cells. That conversion of cells in the esophagus by the
acid reflux, is known as Barrett's Esophagus. Although people who
do not have heartburn can have Barrett's esophagus, it is found
about three to five times more often in people with this condition.
Barrett's esophagus does not cause symptoms itself and is important
only because it seems to precede the development of a particular
kind of cancer--esophageal adenocarcinoma. The risk of developing
adenocarcinoma is 30 to 125 times higher in people who have
Barrett's esophagus than in people who do not. This type of cancer
is increasing rapidly in white men. This increase may be related to
the rise in obesity and GERD.
[0012] Barrett's esophagus has no cure, short of surgical removal
of the esophagus, which is a serious operation. Surgery is
recommended only for people who have a high risk of developing
cancer or who already have it. Most physicians recommend treating
GERD with acid-blocking drugs, since this is sometimes associated
with improvement in the extent of the Barrett's tissue. However,
this approach has not been proven to reduce the risk of cancer.
Treating reflux with a surgical procedure for GERD also does not
seem to cure Barrett's esophagus. Several different experimental
approaches are under study. One attempts to see whether destroying
the Barrett's tissue by heat or other means through an endoscope
can eliminate the condition. This approach, however, has potential
risks and unknown effectiveness.
[0013] Esophageal cancer can occur almost anywhere along the length
of the esophagus, but it frequently starts in the glandular cells
closest to the stomach (adenocarcinoma). Because esophageal cancer
may not be diagnosed until it's quite advanced, the outlook for
people with the disease is often poor. The risk of cancer of the
esophagus is increased by long-term irritation of the esophagus,
such as with smoking, heavy alcohol intake, and Barrett's
esophagitis. Thus, there is a link between esophageal cancer and
bile reflux and acid reflux. In animal models, bile reflux alone
has been shown to cause cancer of the esophagus.
[0014] There are numerous medications available that can
effectively treat heartburn and indigestion. Presently, the main
therapies employed in the treatment of GERD and upper GI tract
disorders include agents for reducing the stomach acidity, for
example by using the histamine Hz-receptor antagonists or proton
pump inhibitors (PPIs). H.sub.2 blockers are drugs that inhibit the
production of acid in the stomach. Exemplary histamine Hz-receptor
antagonists include, for example, cimetidine (as sold under the
brand-name TAGAMET famotidine (as sold under the brand-name PEPCID
AC.RTM.), nizatidine (as sold under the brand-name AXID AR.RTM.),
and ranitidine (as sold under the brand-name ZANTAC 75.RTM.). Both
types of medication are effective in treating heartburn and usually
eliminate symptoms within a short period of time.
[0015] PPIs act by inhibiting the parietal cell H.sup.+/K.sup.+
ATPase proton pumps responsible for acid secretion from these
cells. PPIs, such as omeprazole, and its pharmaceutically
acceptable salts are disclosed, for example, in EP 05129, EP 124495
and U.S. Pat. No. 4,255,431.
[0016] Despite their well-documented efficacy, PPIs have notable
limitations. These drugs exhibit substantial inter-patient
variability in pharmacokinetics and may have significant
interactions with other drugs. For example, patients who are
non-responsive to treatment with PPI inhibitor alone may be
non-responsive because even though the PPI is decreasing acid
reflux from the stomach, bile acid from the duodenum is still
present. Thus, an improvement of PPI-mediated activity is a
well-recognized challenge in gastroenterology and there is a need
in the art to address and overcome upper GI tract disorders that
are non-responsive to treatment by administration of PPIs
alone.
[0017] Accordingly, the development of an effective treatment for
pathologies in which inhibition of one or both of gastric acid
secretion and bile acid secretion is required would be useful.
SUMMARY
[0018] Briefly, the present application discloses a treatment for
upper gastrointestinal disorders in which the inhibition of one or
both of gastric acid secretion and bile acid secretion is
desirable.
[0019] In accordance with the above, the present application
discloses compositions and methods for treating or preventing upper
GI tract disorders such as, for example, gastroesophageal reflux
disease (GERD), heartburn, indigestion, dyspepsia, erosive
esophagitis, peptic ulcer, gastric ulcer, NSAID-associated ulcers,
duodenal ulcers, esophageal ulcers, esophagitis, laryngitis, ulcers
arising from Meckel's diverticulum, Barrett's Esophagus, esophageal
adenocarcinoma, pharyngitis, and GERD-related pulmonary dysfunction
(e.g., asthma and/or cough).
[0020] In a first aspect, compositions containing a therapeutically
effective amount of at least one bile acid sequestrant, wherein the
compositions are useful for treating or preventing an upper GI
tract disorder, or for protecting the stratified squamous
epithelium against injury by a noxious substance, are
disclosed.
[0021] In certain embodiments, the bile acid sequestrant includes,
but is not limited to, cholestyramine (i.e., QUESTRAN.RTM.,
QUESTRAN LIGHT.RTM., CHOLYBAR.RTM., CA registry no. 11041-12-6),
colesevelam (i.e., WELCHOL.RTM., CA registry nos. 182815-43-6 and
182815-44-7), ursodeoxycholic acid (i.e. CA registry no. 128-13-2),
colestipol (i.e., COLESTID.RTM., CA registry nos. 50925-79-6 and
37296-80-3), sevelamer, dialkylaminoalkyl derivatives of a
cross-linked dextran, LOCHOLEST.RTM., DEAE-Sephadex (SECHOLEX.RTM.,
POLIDEXIDE.RTM.), water soluble derivatives such as 3,3-ioene,
N-(cycloalkyl)alkylamines and poliglusam, insoluble quaternized
polystyrenes, saponins and mixtures thereof, those bile acid
sequestrants disclosed in WO97/11345, WO98/57652, U.S. Pat. No.
3,692,895, and U.S. Pat. No. 5,703,188, including pharmaceutically
acceptable salts or mixtures thereof. Suitable inorganic
cholesterol sequestrants include bismuth salicylate plus
montmorillonite clay, aluminum hydroxide and calcium carbonate
antacids.
[0022] In other embodiments, the compositions containing a
therapeutically effective amount of at least one bile acid
sequestrant can additionally include a therapeutically effective
amount of at least one proton pump inhibitor.
[0023] In certain embodiments, the proton pump inhibitor includes,
for example, any of the following compounds: omeprazole (i.e.,
PRILOSEC.RTM., ZEGERID.RTM., LOSEC.RTM., CA registry no.
73590-58-6), esomeprazole (i.e., NEXIUM.RTM., perprazole,
s-omeprazole magnesium, CA registry no. 161973-10-0), lansoprazole
(i.e., PREVACID.RTM., ZOTON.RTM., INHIBITOL.RTM., CA registry no.
103577-45-3), pantoprazole (i.e., PROTONIX.RTM., PROTIUM.RTM.,
SOMAC.RTM., PANTOLOC.RTM., CA registry no. 102625-70-7),
rabeprazole (i.e., RABECID.RTM., ACIPHEX.RTM., PARIET.RTM.,
habeprazole, pariprazole, CA registry nos. 117976-89-3 and
117976-90-6), tenatoprazole (i.e., benatoprazole,
S-Tenatoprazole-Na STU-Na, CA registry no. 113712-98-4),
leminoprazole (i.e., CA registry no. 104340-86-5), dontoprazole
(i.e., CA registry no. 350507-35-6), ransoprazole (i.e., CA
registry no. 832103-67-0), or pharmaceutically acceptable salts or
mixtures thereof.
[0024] In other embodiments, the compositions described herein
(whether prepared as a bile acid sequestrant alone or co-formulated
with a proton pump inhibitor) can be further formulated to
optionally include any one or a combination of the numerous
commercially available, over-the-counter (OTC) medications for
reducing the stomach acidity employed to treat GERD and other upper
GI tract disorders. Such commercially available OTC medications
include, but are not limited to, histamine Hz-receptor antagonists
and antacids.
[0025] Exemplary histamine H2-receptor antagonists include, for
example, cimetidine (as sold under the brand-name TAGAMET HB.RTM.),
famotidine (as sold under the brand-name PEPCID AC.RTM.),
nizatidine (as sold under the brand-name AXID AR.RTM.), and
ranitidine (as sold under the brand-name ZANTAC 75.RTM.).
[0026] Exemplary antacids include, but are not limited to,
insoluble inorganic salts such as calcium carbonate, magnesium
carbonate, calcium hydroxide, magnesium hydroxide, or aluminum
hydroxide. Typical consumer antacid products include, but are not
limited to, TUMS.RTM., MILK of MAGNESIA.RTM., MAALOX PLUS.RTM.,
ALKA-SELTZER.RTM., MYLANTA.RTM., PEPTO-BISMOL.RTM., RIOPAN.RTM.,
and ROLAIDS.RTM..
[0027] In still other embodiments, the compositions described
herein (whether prepared as a bile acid sequestrant alone or
co-formulated with a proton pump inhibitor and another agent) can
be further formulated to optionally include any one or a
combination of .gamma.-aminobutyricacid-b (GABA-B) agonists,
prodrugs of GABA-B agonists, and protease inhibitors.
[0028] Exemplary GABA-B agonists, include, for example, baclofen.
In an embodiment, the GABA-B agonist is R-baclofen.
[0029] Exemplary prodrugs of GABA-B agonists include, for example,
XP19986 (CAS Registry No. 847353-30-4).
[0030] Exemplary protease inhibitors include, for example, aspartyl
protease inhibitors, such as pepstatin and other pepsin inhibitors
(e.g., sodium benzoate); and chymotrypsin and trypsin inhibitors. A
wide variety of trypsin and chymotrypsin inhibitors are known to
those skilled in the art and can be used in the methods described
herein. Such trypsin and chymotrypsin inhibitors can include
tissue-factor-pathway inhibitor; .alpha.-2 antiplasmin; serpin
.alpha.-1 antichymotrypsin family members; gelin; hirustasin;
eglins including eglin C; inhibitors from Bombyx mori (see; e.g.;
JP 4013698 A2 and JP 04013697 A2; CA registry No. 142628-93-1);
hirudin and variants thereof; secretory leukocyte protease
inhibitor (SLPI); .alpha.-1 anti-trypsin; Bowman-Birk protease
inhibitors (BBIs); chymotrypsin inhibitors represented by CAS
registry Nos. 306762-66-3, 306762-67-4, 306762-68-5, 306762-69-6,
306762-70-9, 306762-71-0, 306762-72-1, 306762-73-2, 306762-74-3,
306762-75-4, 178330-92-2, 178330-93-3, 178330-94-4, 81459-62-3,
81459-79-2, 81460-01-7, 85476-59-1, 85476-62-6, 85476-63-7,
85476-67-1, 85476-70-6, 85858-66-8, 85858-68-0, 85858-69-1,
85858-70-4, 85858-71-5, 85858-72-6, 85858-73-7, 85858-75-9,
85858-77-1, 85858-79-3, 85858-81-7, 85858-83-9, 85858-84-0,
85858-85-1, 85858-87-3, 85858-89-5, 85858-90-8, 85858-92-0,
85879-03-4, 85879-05-6, 85879-06-7, 85879-08-9, 85858-74-8,
90186-24-6, 90185-93-6, 89703-10-6, 138320-33-9 (YS3025),
94149-41-4 (MR889), 85858-76-0, 89703-10-6, 90185-92-5, 90185-96-9,
90185-98-1, 90186-00-8, 90186-01-9, 90186-05-3, 90186-06-4,
90186-07-5, 90186-08-6, 90186-09-7, 90186-10-0, 90186-11-1,
90186-12-2, 90186-13-3, 90186-14-4, 90186-22-4, 90186-23-5,
90186-24-6, 90186-25-7, 90186-27-9, 90186-28-0, 90186-29-1,
90186-31-5, 90186-35-9, 90186-43-9, 90209-88-4, 90209-89-5,
90209-92-0, 90209-94-2, 90209-96-4, 90209-97-5, 90210-01-8,
90210-03-0, 90210-04-1, 90210-25-6, 90210-26-7, 90210-28-9,
90230-84-5, 90409-84-0, 95460-86-9, 95460-87-0, 95460-88-1,
95460-89-2, 95460-91-6, 114949-00-7, 114949-01-8, 114949-02-9,
114949-03-0, 114949-04-1, 114949-05-2, 114949-06-3, 114949-18-7,
114949-19-8, 114964-69-1, 114964-70-4, 9076-44-2 (chymostatin),
30827-99-7 (Pefabloc), 618-39-3 (benzamidine), 80449-31-6
(urinistatin), 130982-43-3, 197913-52-3, 179324-22-2, 274901-16-5,
792163-40-7, 339169-59-4, 243462-36-4, 654671-78-0, 55123-66-5
(leupeptin), 901-47-3, 4272-74-6, 51050-59-0, 221051-66-7,
80449-31-6, 55-91-4, 60-32-2, 88070-98-8, 87928-05-0, 402-71-1
(benzenesulfonamide), 139466-47-0, CI-2A (see U.S. Pat. No.
5,167,483), CI-2A (seebWO9205239), WCI-3 (see Shibata et al. 1988 J
Biochem (Tokyo) 104:537-43), WCI-2 (see Habu et al. 1992 J Biochem
(Tokyo) 111:249-58), and WCI-x (Habu et al., supra) and
178330-95-5; and compounds with chymotrypsin inhibition activity
described in patent publications JP 56092217 A2, U.S. Pat. No.
4,755,383, U.S. Pat. No. 4,755,383, U.S. Pat. No. 4,639,435, U.S.
Pat. No. 4,620,005, U.S. Pat. No. 4,898,876, and EP0128007.
[0031] In a second aspect, pharmaceutical compositions for gastric
retention of any of the compositions described herein are disclosed
and provide sustained-release of the active agents. In certain
embodiments, the pharmaceutical dosage form contains at least one
bile acid sequestrant and a gastric-retention vehicle composition
that contains one or more hydrogels such that the dosage form
expands upon contact with gastric fluid.
[0032] In certain embodiments, the pharmaceutical dosage form is
retained for a period of 6-24 hours (e.g., 6, 7, 8, 9, 10, 11, 12,
13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours), or
longer.
[0033] In certain embodiments, the active agent component can be in
the form of a tablet and may additionally contain suitable
diluents, glidants, lubricants, acidulants, stabilizers, swelling
agents and other pharmaceutically acceptable excipients.
[0034] Exemplary hydrogels include, for example, hydroxypropyl
methylcellulose, hydroxypropylcellulose, sodium
carboxymethylcellulose, agar, agarose, locust bean gum, carageenan,
alginic acid, konjac gum, guar gum, and xanthan gum.
[0035] In other embodiments, the gastric-retention vehicle
composition can additionally include one or more of a
superdisintegrant, a binder, and a gas-generating agent.
[0036] Exemplary superdisintegrants include, for example,
crospovidone, croscarmellose sodium, and sodium starch
glycolate.
[0037] Exemplary binders include, for example, poloxamers,
polyethylene glycols, polyethylene glycol fatty acid esters,
glyceryl palmitostearate, polyoxyethylene alkyl ethers, glyceryl
behenate, stearoyl macrogol-32-glyceride, polyoxyethylene castor
oil derivatives, polyoxyethylene sorbitan fatty acid derivatives,
polyoxyethylene stearates, polyoxyethylene-polyoxypropylene
copolymers, starches, gelatin, sugars such as lactose, sucrose,
glucose and molasses, natural and synthetic gums such as acacia,
sodium alginate, carboxymethylcellulose, methylcellulose,
polyvinylpyrrolidone, ethyl cellulose and waxes.
[0038] Exemplary gas-generating agents include, for example, sodium
hydrogen carbonate, sodium carbonate, potassium carbonate, calcium
carbonate, magnesium carbonate, and sodium glycine carbonate.
[0039] In a third aspect, methods for treating or preventing an
upper gastrointestinal tract disorder by administering to a patient
in need thereof a composition containing a therapeutically
effective amount of at least one bile acid sequestrant are
disclosed.
[0040] In certain embodiments, the patient may be suffering from
(or susceptible to developing) an upper GI tract disorder
including, but not limited to, dyspepsia, heartburn, erosive
esophagitis GERD, peptic ulcer, esophagitis, Barrett's Esophagus,
and esophageal adenocarcinoma.
[0041] In other embodiments, the methods can include administering
simultaneously, separately, or sequentially, a therapeutically
effective amount of one or more proton pump inhibitors.
[0042] In still other embodiments, the methods can include
administering simultaneously, separately, or sequentially one or
more agents chosen from an antacid, a histamine Hz-receptor
antagonist, a .gamma.-aminobutyricacid-b (GABA-B) agonist, a
prodrug of a GABA-B agonist, and a protease inhibitor.
[0043] In other embodiments, the composition is in a form suitable
for oral administration.
[0044] In another aspect, methods for protecting stratified
squamous epithelium against injury by a noxious substance by
administering to an individual in need thereof a therapeutically
effective amount of a composition comprising at least one bile acid
sequestrant are disclosed.
[0045] In certain embodiments, the methods can include
administering simultaneously, separately, or sequentially, a
therapeutically effective amount of one or more proton pump
inhibitors.
[0046] In other embodiments, the methods can include administering
simultaneously, separately, or sequentially one or more agents
chosen from an antacid, a histamine Hz-receptor antagonist, a
.gamma.-aminobutyricacid-b (GABA-B) agonist, a prodrug of a GABA-B
agonist, and a protease inhibitor.
[0047] In yet another aspect, kits for treating an upper GI tract
disorder comprising, in one or more containers, a therapeutically
effective amount of the compositions as described in detail herein,
and a label or packaging insert containing instructions for use are
disclosed.
[0048] These, and other objects, features and advantages of this
disclosure will become apparent from the following detailed
description of the various aspects of the disclosure taken in
conjunction with the accompanying Examples.
DETAILED DESCRIPTION
[0049] The present application discloses compositions containing at
least one bile acid sequestrant, alone or in combination with other
active agents, which are useful for treating or preventing a
variety of upper gastrointestinal (GI) tract disorders and
associated conditions.
[0050] The present application further discloses compositions
including at least one proton pump inhibitor and at least one bile
acid sequestrant which when administered to esophageal epithelial
cell cultures, which are normally nonkeratinized, stratified
squamous epithelium arranged in longitudinal folds, provide the
benefit of inhibiting transformation into specialized columnar
cells (indicating premalignancy) at a greater efficacy than either
agent alone.
[0051] Accordingly, the compositions disclosed herein are useful in
methods for treating or preventing a variety of upper
gastrointestinal (GI) tract disorders and associated conditions
such as, for example, gastroesophageal reflux disease (GERD)
(including non-responsive GERD), heartburn, indigestion, dyspepsia,
erosive esophagitis, peptic ulcer, gastric ulcer, NSAID-associated
ulcers, duodenal ulcers, esophageal ulcers, esophagitis,
laryngitis, ulcers arising from Meckel's diverticulum, Barrett's
Esophagus, esophageal adenocarcinoma, and pharyngitis.
[0052] The present application includes compositions comprising
therapeutically effective amounts of at least one bile acid
sequestrant, or pharmaceutically acceptable salts thereof,
formulated alone or in combination with a therapeutically effective
amount of at least one proton pump inhibitor, or pharmaceutically
acceptable salts thereof. In an embodiment, the compositions
disclosed herein can also include, or be administered in
combination (either simultaneously, separately, or sequentially)
with, one or more commercially available antacids, histamine
Hz-receptor antagonists, .gamma.-aminobutyricacid-b (GABA-B)
agonists, prodrugs of GABA-B agonists, and protease inhibitors.
[0053] In certain embodiments, any of the compositions disclosed
herein can be provided as a sustained-release pharmaceutical dosage
form that includes a therapeutically effective amount of one of the
compositions described herein and a gastric-retention vehicle
composition that contains one or more hydrogels, such that the
dosage form expands upon contact with gastric fluid, thereby
retaining the dosage form in the user's stomach for a longer period
of time.
[0054] The present application also includes methods for treating
or preventing an upper GI tract disorder by administering to a
patient in need thereof a therapeutically effective amount of a
pharmaceutical composition as disclosed and described in detail
herein.
[0055] Similarly, the present application also includes methods for
protecting stratified squamous epithelium against injury by a
noxious substance by administering to a patient in need thereof a
therapeutically effective amount of a pharmaceutical composition as
disclosed and described in detail herein.
[0056] As employed above and throughout the disclosure, the
following terms are provided to assist the reader. Unless otherwise
defined, all terms of art, notations and other scientific or
medical terms or terminology used herein are intended to have the
meanings commonly understood by those of skill in the chemical and
medical arts. In some cases, terms with commonly understood
meanings are defined herein for clarity and/or for ready reference,
and the inclusion of such definitions herein should not necessarily
be construed to represent a substantial difference over the
definition of the term as generally understood in the art unless
otherwise indicated.
[0057] As used herein, "treating" or "treatment of" a condition or
subject refers to taking steps to obtain beneficial or desired
results, including clinical results. For purposes of this
disclosure, beneficial or desired clinical results include, but are
not limited to, alleviation or amelioration of one or more disease,
symptom, or condition related to lipid metabolism disorders, fatty
liver disease, hepatitis, or erectile dysfunction.
[0058] As used herein, a "therapeutically effective amount" of a
drug or pharmaceutical composition or formulation, or agent,
described herein is an amount of a drug or agent that, when
administered to a subject with a disease or condition, will have
the intended therapeutic effect, e.g., alleviation, amelioration,
palliation or elimination of one or more manifestations of the
disease or condition in the subject. The full therapeutic effect
does not necessarily occur by administration of one dose and may
occur only after administration of a series of doses. Thus, a
therapeutically effective amount may be administered in one or more
administrations.
[0059] As used herein, a "prophylactically effective amount" of a
drug or pharmaceutical composition or formulation, or agent,
described herein is an amount of a drug or agent that, when
administered to a subject, will have the intended prophylactic
effect, e.g., preventing or delaying the onset (or reoccurrence) of
disease or symptoms, or reducing the likelihood of the onset (or
reoccurrence) of disease or symptoms. The full prophylactic effect
does not necessarily occur by administration of one dose and may
occur only after administration of a series of doses. Thus, a
prophylactically effective amount may be administered in one or
more administrations.
[0060] As used herein, and as would be understood by the person of
skill in the art, the recitation of "a compound" or "a composition"
is intended to include salts, solvates and inclusion complexes of
that compound as well as any stereoisomeric form, or a mixture of
any such forms of that compound in any ratio.
[0061] The term "pharmaceutically acceptable salt" refers to salts
prepared from pharmaceutically acceptable non-toxic acids or bases
including inorganic acids and bases and organic acids and bases.
When the compounds of the present disclosure are basic, salts may
be prepared from pharmaceutically acceptable non-toxic acids
including inorganic and organic acids. Suitable pharmaceutically
acceptable acid addition salts for the compounds of the present
disclosure include acetic, benzenesulfonic (besylate), benzoic,
camphorsulfonic, citric, ethenesulfonic, fumaric, gluconic,
glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic,
malic, mandelic, methanesulfonic, mucic, nitric, pamoic,
pantothenic, phosphoric, succinic, sulfuric, tartaric acid,
p-toluenesulfonic, and the like. When the compounds contain an
acidic side chain, suitable pharmaceutically acceptable base
addition salts for the compounds of the present disclosure include
metallic salts made from aluminum, calcium, lithium, magnesium,
potassium, sodium and zinc or organic salts made from lysine,
N,N'-dibenzylethylenediamine, chloroprocaine, choline,
diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and
procaine.
[0062] Administration of any of the compositions or formulations
described in detail herein includes parallel administration (i.e.,
administration of elements of the formulation to the subject over a
period-of time), co-administration or sequential administration (in
which elements of the formulation are administered at approximately
the same time, e.g., within about a few seconds to a few hours of
one another), and simultaneous or co-formulation (in which elements
of the formulation are combined or compounded into a single dosage
form suitable for oral or parenteral administration).
[0063] Combination therapy can be achieved by administering two or
more agents, e.g., a proton pump inhibitor and a bile acid
sequestrant, each of which is formulated and administered
separately, or by administering two or more agents in a single
formulation. Other combinations are also encompassed by combination
therapy. For example, two agents can be formulated together and
administered in conjunction with a separate formulation containing
a third agent. While the two or more agents in the combination
therapy can be administered simultaneously, they need not be. For
example, administration of a first agent (or combination of agents)
can precede administration of a second agent (or combination of
agents) by minutes, hours, days, or weeks. Thus, the two or more
agents can be administered within minutes of each other or within
1, 2, 3, 6, 9, 12, 15, 18, or 24 hours of each other or within 1,
2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14 days of each other or within 2,
3, 4, 5, 6, 7, 8, 9, or 10 weeks of each other. In some cases even
longer intervals are possible. While in many cases it is desirable
that the two or more agents used in a combination therapy be
present in within the patient's body at the same time, this need
not be so.
[0064] Combination therapy can also include two or more
administrations of one or more of the agents used in the
combination. For example, if agent X and agent Y are used in a
combination, one could administer them sequentially in any
combination one or more times, e.g., in the order X-Y-X, X-X-Y,
Y-X-Y, Y-Y-X, X-X-Y-Y, etc.
[0065] A "subject" or "patient" is a mammal, preferably a human,
but can also be an animal in need of veterinary treatment, e.g.,
companion animals (e.g., dogs, cats, and the like), farm animals
(e.g., cows, sheep, pigs, horses, and the like) and laboratory
animals (e.g., rats, mice, guinea pigs, and the like).
[0066] A "susceptible individual" or "patient in need thereof" is
an individual who suffers from, is suffering from, or is likely to
or predisposed to suffer from an upper GI tract disorder. In humans
these conditions may include, for example, gastroesophageal reflux
disease (GERD), heartburn, indigestion, dyspepsia, erosive
esophagitis, peptic ulcer, gastric ulcer, NSAID-associated ulcers,
duodenal ulcers, esophageal ulcers, esophagitis, laryngitis,
Meckel's diverticulum, Barrett's Esophagus, esophageal
adenocarcinoma, or pharyngitis. In animals these conditions may
include, for example, peptic ulcer of the forestomach.
[0067] As used herein "non-responsive GERD" refers to chronic
reflux disorders that do not respond to current therapies used to
treat such conditions. Such therapies include, for example,
administration of proton pump inhibitors, H.sub.2 blockers, and
various antacids that are well known in the art.
[0068] A "noxious substance", as used herein, refers to a substance
which causes injury to stratified squamous epithelium in vivo.
Examples of such "noxious substances" include acids or other
substances, including, but not limited to, gastric acid, HCl,
N-acetylcysteine, pepsin, acid-pepsin, or other irritant which
contacts epithelial tissue.
[0069] The terms "gastric fluid" and "gastric juice" are used
interchangeably throughout and refer to the endogenous fluid medium
of the stomach, including water and secretions. "Simulated gastric
fluid" means any fluid that is generally recognized as providing a
useful substitute for authentic gastric fluid in experiments
designed to assess the chemical or biological behavior of
substances in the stomach. One such simulated gastric fluid is
aqueous 0.1 N HCl, pH 1.2. It will be understood that the term
"gastric fluid" or "gastric juice" used throughout the disclosure
and claims means authentic (i.e. endogenous) gastric fluid or
simulated gastric fluid.
[0070] The term "gastro-retentive form" or "gastric retention
vehicle" denotes dosage forms which effect sustained release of the
active ingredient in comparison with conventional dosage forms,
such as customary tablets or capsules, while avoiding an
undesirably high initial dose, the release being effected
continuously over a relatively long period and controlled at a
therapeutically effective level by prolonged retention of the
dosage form in the stomach.
[0071] This present disclosure provides, in various embodiments,
pharmaceutical combination kits and oral drug dosage forms that
contain at least one bile acid sequestrant alone or in combination
with at least one proton pump inhibitor, optionally comprising one
or more additional agents chosen from an antacid, a histamine
Hz-receptor antagonist, a .gamma.-aminobutyricacid-b (GABA-B)
agonist, a prodrug of a GABA-B agonist, and a protease inhibitor.
These agents may be contained in the same oral dosage form or in
separate dosage forms that are administered sequentially or
simultaneously.
[0072] The present disclosure also relates to a method for treating
or preventing an upper gastrointestinal tract disorder, which is
particularly useful as a first-line or initial therapy, comprising
administering to a patient in need thereof a combination
therapeutic regimen as described in the kits and dosage forms
provided and discussed herein. "First-line" or "initial" treatment
refers to treatment in the first instance after a new diagnosis of
an upper gastrointestinal tract disorder, or after a relapse of an
upper gastrointestinal tract disorder following cessation of
treatment. However, the treatment method can be useful in any upper
gastrointestinal tract disorder patient who is not responding to
monotherapy with PPIs or bile acid sequestrants.
[0073] PPI drugs are substituted benzimidazole compounds that
specifically inhibit gastric acid secretion by affecting the
H.sup.+/K.sup.+ ATPase enzyme system (the proton pump). These
drugs, for example esomeprazole, are rapidly absorbed and have very
short half-lives. However, they exhibit prolonged binding to the
H.sup.+/K.sup.+ ATPase enzyme. The anti-secretory effect reaches a
maximum in about 4 days with once-daily dosing. Because of these
characteristics, patients beginning PPI therapy do not receive
maximum benefit of the drug and healing may not begin for up to 5
days after therapy begins when PPIs are used alone for initial
therapy of upper GI tract disorders.
[0074] Proton pump inhibitors (PPIs) are potent inhibitors of
gastric acid secretion, inhibiting H.sup.+/K.sup.+ ATPase, the
enzyme involved in the final step of hydrogen ion production in the
parietal cells. The term proton pump inhibitor includes, but is not
limited to, omeprazole (as sold under the brand-names
PRILOSEC.RTM., LOSEC.RTM., or ZEGERID.RTM.), lansoprazole (as sold
under the brand-name PREVACID.RTM., ZOTON.RTM., or INHIBITOL.RTM.),
rabeprazole (as sold under the brand-name RABECID.RTM.,
ACIPHEX.RTM., or PARIET.RTM.), pantoprazole (as sold under the
brand-name PROTONIX.RTM., PROTIUM.RTM., SOMAC.RTM., or
PANTOLOC.RTM.), tenatoprazole (also referred to as benatoprazole),
and leminoprazole, including isomers, enantiomers and tautomers
thereof (e.g., esomeprazole (as sold under the brand-name
NEXIUM.RTM.)), and alkaline salts thereof. The following patents
describe various benzimidazole compounds suitable for use in the
disclosure described herein: U.S. Pat. No. 4,045,563, U.S. Pat. No.
4,255,431, U.S. Pat. No. 4,359,465, U.S. Pat. No. 4,472,409, U.S.
Pat. No. 4,508,905, JP-A-59181277, U.S. Pat. No. 4,628,098, U.S.
Pat. No. 4,738,975, U.S. Pat. No. 5,045,321, U.S. Pat. No.
4,786,505, U.S. Pat. No. 4,853,230, U.S. Pat. No. 5,045,552,
EP-A-295603, U.S. Pat. No. 5,312,824, EP-A-166287, U.S. Pat. No.
5,877,192, EP-A-519365, EP5129, EP 174,726, EP 166,287 and GB
2,163,747. All of the above patents are hereby incorporated herein
by reference. Thus, proton pump inhibitors and their
pharmaceutically acceptable salts, which are used in accordance
with the present disclosure, are known compounds and can be
produced by known processes. In certain embodiments, the proton
pump inhibitor is omeprazole, either in racemic mixture or only the
(-)enantiomer of omeprazole (i.e. esomeprazole), as set forth in
U.S. Pat. No. 5,877,192, hereby incorporated by reference.
[0075] Omeprazole is typically administered in a 20 mg dose/day for
active duodenal ulcer for 4-8 weeks; in a 20 mg dose/day for
gastro-esophageal reflux disease (GERD) or severe erosive
esophagitis for 4-8 weeks; in a 20 mg dose/twice a day for
treatment of Helicobacter pylori (in combination with other
agents); in a 60 mg dose/day for active duodenal ulcer for 4-8
weeks and up to 120 mg three times/day, and in a 40 mg dose/day for
gastric ulcer for 4-8 weeks. Such dosages are contemplated to be
within the scope of the present disclosure. Thus, in certain
embodiments of the present disclosure, the amount of proton pump
inhibitor which is included in the dosage form is an amount which
is considered to be therapeutically effective, in accordance with
the dosages set forth above for a variety of disease states. In
other embodiments of the present disclosure, the dose of proton
pump inhibitor is sub-therapeutic. For example, when the drug is
omeprazole, the dosage form may contain from about 0.1 mg to about
120 mg omeprazole.
[0076] Lansoprazole is typically administered about 15-30 mg/day;
rabeprazole is typically administered 20 mg/day and pantoprazole is
typically administered 40 mg/day. However, any therapeutic or
sub-therapeutic dose of these agents is considered within the scope
of the present disclosure.
[0077] In certain embodiments, the proton pump inhibitor(s)
included in the dosage forms of the present disclosure are
protected from contact with acidic gastric juice, and transferred
without exposure to gastric fluid until the dosage form reaches a
part of the gastrointestinal tract where the pH is near neutral and
where rapid absorption of omeprazole can occur.
[0078] Bile acids are steroid acids found predominantly in the bile
of mammals. They are produced in the liver by the oxidation of
cholesterol, and are stored in gallbladder and secreted into the
intestine in the form of salts. They act as surfactants,
emulsifying lipids and assisting with the absorption and digestion
of dietary fat and cholesterol.
[0079] Synthesis of bile acids is a major consumer of cholesterol.
The body synthesizes about 800 mg of cholesterol per day and about
half of that is used for bile acid synthesis. In total about 20-30
grams of bile acids are secreted into the intestine daily; about
90% of excreted bile acids are reabsorbed (by active transport in
the ileum) and recycled. This is referred to as the enterohepatic
circulation.
[0080] Since bile acids are made from endogenous cholesterol, the
enterohepatic circulation of bile acids may be disrupted as a way
to lower cholesterol. This is the usual therapeutic rationale for
administering bile acid sequestrants.
[0081] The principal bile acids are: Cholic acid, Chenodeoxycholic
acid, Deoxycholic acid, Taurocholic acid, and Glycocholic acid. The
chemical distinctions between different bile acids are minute,
depending only on the presence or absence of hydroxyl groups on
positions 3, 7, and 12. In humans, the most important bile acids
are cholic acid and chenodeoxycholic acid, and their conjugates
with taurine and glycine (glycocholate and taurocholate). Some
mammals synthesize predominantly deoxycholic acid.
[0082] As surfactants or detergents, bile acids are potentially
toxic to cells and their levels are tightly regulated. They
function directly as signaling molecules in the liver and the
intestines by activating a nuclear hormone receptor known as FXR
and also NR1H4. This results in inhibition of bile acid synthesis
in the liver when bile acid levels are too high. Emerging evidence
associates FXR activation with alterations in triglyceride
metabolism, glucose metabolism and liver growth.
[0083] Bile acid sequestrants bind bile acids in the small
intestine and carry them out of the body. This causes the body to
use more cholesterol to make more bile acids, which are secreted
into the small intestine, bound to bile acid sequestrants, and
carried out of the body. The end result is lower cholesterol
levels. Bile acid sequestrants also prevent absorption of some
dietary cholesterol.
[0084] Bile acid sequestrants currently approved for human use are
polymeric compounds which serve as ion exchange resins. Bile acid
sequestrants exchange anions such as chloride ions for bile acids.
By doing so, they bind bile acids and sequester them from
enterohepatic circulation. Since bile acid sequestrants are large
polymeric structures, they are not well-absorbed from the gut into
the bloodstream. Thus, bile acid sequestrants, along with any bile
acids bound to the drug, are excreted via the feces after passage
through the gastrointestinal tract. Exemplary bile acid
sequestrants include, for example, cholestyramine (as sold under
the brand-name QUESTRAN.RTM.), colesevelam (as sold under the
brand-name WELCHOL.RTM.), and colestipol (as sold under the
brand-name COLESTID.RTM.), and pharmaceutically acceptable salts
thereof.
[0085] The present disclosure is also directed to a dosage form
that provides for the release of at least one bile acid sequestrant
to reduce bile acid reflux symptoms in a patient, as well as for
the release of both at least one bile acid sequestrant and at least
one proton pump inhibitor to reduce both bile acid reflux and
gastric acid reflux symptoms in a patient. The dosage form can be
prepared such that the active ingredients are for quick release or
delayed release, or quick release of one active ingredient and
delayed release of the other active ingredient.
[0086] The compositions comprising the active agents disclosed
herein may also be formulated to include, or administered in
conjunction with, other agents for treating the gastrointestinal
tract, such as histamine H.sub.2 receptor blockers, motility agents
(gastroprokinetics), antacids, antiulcerative agents,
.gamma.-aminobutyricacid-b (GABA-B) agonists, prodrugs of GABA-B
agonists, and/or protease inhibitors. Nonlimiting examples of these
additional agents include those selected from the group consisting
of cinitapride, cisapride, fedotozine, loxiglumide, alexitol
sodium, almagate, aluminum hydroxide, aluminum magnesium silicate,
aluminum phosphate, azulene, basic aluminum carbonate gel, bismuth
aluminate, bismuth phosphate, bismuth subgallate, bismuth
subnitrate, calcium carbonate, dihydroxyaluminum aminoacetate,
dihydroxyaluminum sodium carbonate, ebimar, magaldrate, magnesium
carbonate hydroxide, magnesium hydroxide, magnesium oxide,
magnesium peroxide, magnesium phosphate (tribasic), magnesium
silicates, potassium citrate, sodium bicarbonate, aceglutamide
aluminum complex, acetoxolone, aldioxa, arbaprostil, benexate
hydrochloride, carbenoxolone, cetraxate, cimetidine, colloidal
bismuth subcitrate, ebrotidine, ecabet, enprostil, esaprazole,
famotidine, gefamate, guaiazulene, irsogladine, misoprostol,
nizatidine, omoprostil, .gamma.-Oryzanol, pifamine, pirenzepine,
plaunotol, polaprezinc, ranitidine, rebamipide, rioprostil,
rosaprostol, rotraxate, roxatidine acetate, sofalcone, spizofarone,
sucralfate, telenzepine, teprenone, trimoprostil, trithiozine,
troxipide, zolimidine, baclofen, R-baclofen, XP19986 (CAS Registry
No. 847353-30-4), pepstatin and other pepsin inhibitors (e.g.,
sodium benzoate); and chymotrypsin and trypsin inhibitors. A wide
variety of trypsin and chymotrypsin inhibitors are known to those
skilled in the art and can be used in the methods described herein.
Such trypsin and chymotrypsin inhibitors can include
tissue-factor-pathway inhibitor; .alpha.-2 antiplasmin; serpin
.alpha.-1 antichymotrypsin family members; gelin; hirustasin;
eglins including eglin C; inhibitors from Bombyx mori (see; e.g.;
JP 4013698 A2 and JP 04013697 A2; CA registry No. 142628-93-1);
hirudin and variants thereof; secretory leukocyte protease
inhibitor (SLPI); .alpha.-1 anti-trypsin; Bowman-Birk protease
inhibitors (BBIs); chymotrypsin inhibitors represented by CAS
registry Nos. 306762-66-3, 306762-67-4, 306762-68-5, 306762-69-6,
306762-70-9, 306762-71-0, 306762-72-1, 306762-73-2, 306762-74-3,
306762-75-4, 178330-92-2, 178330-93-3, 178330-94-4, 81459-62-3,
81459-79-2, 81460-01-7, 85476-59-1, 85476-62-6, 85476-63-7,
85476-67-1, 85476-70-6, 85858-66-8, 85858-68-0, 85858-69-1,
85858-70-4, 85858-71-5, 85858-72-6, 85858-73-7, 85858-75-9,
85858-77-1, 85858-79-3, 85858-81-7, 85858-83-9, 85858-84-0,
85858-85-1, 85858-87-3, 85858-89-5, 85858-90-8, 85858-92-0,
85879-03-4, 85879-05-6, 85879-06-7, 85879-08-9, 85858-74-8,
90186-24-6, 90185-93-6, 89703-10-6, 138320-33-9 (YS3025),
94149-41-4 (MR889), 85858-76-0, 89703-10-6, 90185-92-5, 90185-96-9,
90185-98-1, 90186-00-8, 90186-01-9, 90186-05-3, 90186-06-4,
90186-07-5, 90186-08-6, 90186-09-7, 90186-10-0, 90186-11-1,
90186-12-2, 90186-13-3, 90186-14-4, 90186-22-4, 90186-23-5,
90186-24-6, 90186-25-7, 90186-27-9, 90186-28-0, 90186-29-1,
90186-31-5, 90186-35-9, 90186-43-9, 90209-88-4, 90209-89-5,
90209-92-0, 90209-94-2, 90209-96-4, 90209-97-5, 90210-01-8,
90210-03-0, 90210-04-1, 90210-25-6, 90210-26-7, 90210-28-9,
90230-84-5, 90409-84-0, 95460-86-9, 95460-87-0, 95460-88-1,
95460-89-2, 95460-91-6, 114949-00-7, 114949-01-8, 114949-02-9,
114949-03-0, 114949-04-1, 114949-05-2, 114949-06-3, 114949-18-7,
114949-19-8, 114964-69-1, 114964-70-4, 9076-44-2 (chymostatin),
30827-99-7 (Pefabloc), 618-39-3 (benzamidine), 80449-31-6
(urinistatin), 130982-43-3, 197913-52-3, 179324-22-2, 274901-16-5,
792163-40-7, 339169-59-4, 243462-36-4, 654671-78-0, 55123-66-5
(leupeptin), 901-47-3, 4272-74-6, 51050-59-0, 221051-66-7,
80449-31-6, 55-91-4, 60-32-2, 88070-98-8, 87928-05-0, 402-71-1
(benzenesulfonamide), 139466-47-0, CI-2A (see U.S. Pat. No.
5,167,483), CI-2A (seebWO9205239), WCI-3 (see Shibata et al. 1988 J
Biochem (Tokyo) 104:537-43), WCI-2 (see Habu et al. 1992 J Biochem
(Tokyo) 111:249-58), and WCI-x (Habu et al., supra) and
178330-95-5; and compounds with chymotrypsin inhibition activity
described in patent publications JP 56092217 A2, U.S. Pat. No.
4,755,383, U.S. Pat. No. 4,755,383, U.S. Pat. No. 4,639,435, U.S.
Pat. No. 4,620,005, U.S. Pat. No. 4,898,876, and EP0128007.
[0087] The active ingredients used in tablets, i.e., bile acid
sequestrants alone or in combination with proton pump inhibitors,
are well known in the art and many are commercially available. If
desired, drugs can also be manufactured using methodology well
known in the art.
Formulation and Administration
[0088] Making of Pharmaceutical Preparations: The active agents
used in the compositions of the present disclosure will typically
be formulated in accordance with methods that are standard in the
art (see e.g., Remington: the Science and Practice of Pharmacy 19th
Ed. 1995 Mack Publishing Co. Easton Pa.). Drugs may be prepared in
admixture with conventional excipients, carriers, buffers,
flavoring agents, etc. Typical carriers include, but are not
limited to: water; salt solutions; alcohols; gum arabic; vegetable
oils; benzyl alcohols; polyethylene glycols; gelatin;
carbohydrates, such as lactose, amylose or starch; magnesium
stearate; talc; silicic acid; paraffin; perfume oil; fatty acid
esters; hydroxymethylcellulose; polyvinyl pyrrolidone; etc.
Pharmaceutical preparations can be sterilized and, if desired,
mixed with auxiliary agents such as: lubricants; preservatives;
disintegrants; stabilizers such as cyclodextrans; wetting agents;
emulsifiers; salts; buffers; natural or artificial coloring agents;
natural or artificial flavoring agents; or aromatic substances.
Pharmaceutical preparations can also include one or more of the
following: acetylated monoglyceride, aspartame, beta carotene,
calcium stearate, carnauba wax, cellulose acetate phthalate, citric
acid, citric acid anhydrous, colloidal silicon dioxide,
confectioner's sugar, crospovidone, docusate sodium, ethyl alcohol,
ferric oxide, fructose, gelatin, glycerine, glyceryl monostearate
(e.g. glyceryl monostearate 40-50), glyceryl triacetate, HPMC
(hydroxypropyl methylcellulose), hydroxypropyl cellulose,
hypromellose, iron oxide, isopropyl alcohol, lactose monohydrate,
low substituted hydroxypropyl cellulose, magnesium carbonate,
magnesium stearate, maltol, mannitol, methacrylic acid, methacrylic
acid copolymer (e.g. methacrylic acid copolymer type C),
methylcellulose, microcrystalline cellulose, mono ammonium
glycyrrhizinate, n-butyl alcohol, paraffin, pectin propylene glycol
alginate, polyacrylate, polyethylene glycol (e.g. polyethylene
glycol 6000), polysorbate 80, polyvinyl pyrrolidone, povidone,
propylene glycol, shellac, silicon dioxide, sodium carbonate,
sodium citrate, sodium hydroxide, sodium lauryl sulfate, sodium
stearyl fumarate, sorbitol, starch, sucrose, sugar sphere, talc,
titanium dioxide, triethyl citrate, and xanthan gum. In certain
embodiments, buffers that can raise the pH of the stomach are used.
For example bicarbonate buffers may be included in the outer
coating or as a rapidly dissolving, separate layer immediately
below the outer coating.
[0089] The enteric coating surrounding the core may be applied
using standard coating techniques. Materials used to form the
enteric coating may be dissolved or dispersed in organic or aqueous
solvents and may include one or more of the following: methacrylic
acid copolymers; shellac; hydroxypropylmethylcellulose phthalate;
polyvinyl acetate phthalate; hydroxypropylmethylcellulose
trimellitate; carboxymethylcellulose; cellulose acetate phthalate;
or other suitable enteric coating polymers. The pH at which the
enteric coat will dissolve can be controlled by the polymer or
combination of polymers selected and/or ratio of pendant groups.
For example, dissolution characteristics of the coating can be
altered by the ratio of free carboxyl groups to ester groups.
Enteric coating layers may also contain pharmaceutical plasticizers
such as: triethyl citrate; dibutyl phthalate; triacetin;
polyethylene glycols; polysorbates; etc. Additives such as
dispersants, colorants, anti-adhering and anti-foaming agents may
also be included.
[0090] Making of Tablet Dosage Forms: Tablets can be made using
standard technology well known in the art. Drugs used in the core
or the outer coating may be granulated by methods such as slugging,
low-shear or high-shear granulation, wet granulation, or fluidized
bed granulation. Outer coatings may be formed by preparing a
mixture containing appropriate polymers and a sufficient amount of
drug to produce a therapeutically effective dose. The solution may
then be sprayed on preformed, enterically-coated cores to produce
the final tablets. If desired, a buffer layer or layer containing
other agents may be interspersed between the enterically coated
core and the outer coating.
[0091] In certain embodiments a pharmaceutical composition is
prepared by adding a pharmaceutically acceptable carrier to the
aforementioned compound, a pharmaceutically acceptable salt
thereof, or a hydrate thereof as an active ingredient of the
medicament of the present disclosure. As the medicament of the
present disclosure, a substance, per se, that is selected from the
group consisting of the alkylenedioxybenzene derivative and a
pharmaceutically acceptable salt thereof, and a hydrate thereof and
a solvate thereof may be administered to a mammal including human.
In certain embodiments, pharmaceutical compositions comprising one
or more of the aforementioned substances as an active ingredient
and one or more of pharmaceutical additives are administered to a
patient.
[0092] A variety of administration routes can be used in accordance
with the present disclosure. An effective amount of the peptide
described herein can be administered parenterally, orally, by
inhalation, nasally, buccally, or via an implanted reservoir.
[0093] Examples of the pharmaceutical composition include
formulations for oral administration such as tablets, capsules,
subtilized granules, powders, pills, troches, sublingual tablets
and liquid preparations, and formulations for parenteral
administration such as injections, suppositories, ointments,
patches and the like.
[0094] In certain embodiments, formulations including those which
slowly release the agent over time, such as found in lozenges,
gums, and buccal patches are used. In other embodiments,
formulations including agents in a bioadherent ingestible
composition, such as those found in U.S. Pat. Nos. 5,858,391 and
5,670,163 to Cuca, et al. are used. The agent may also be
formulated as a liquid or as a tablet, pill, capsule or powder to
be dissolved in a liquid, and is preferably slowly sipped by the
patient.
[0095] The protective agents disclosed herein and compositions
comprising the agents may be administered by perfusion via a tube
on to the surface of stratified squamous epithelia, by oral
ingestion, gum or lozenge (for treatment of oropharyngeal, rumen,
forestomach and esophageal epithelium), by mouth rinse (for
oropharyngeal, tongue and buccal epithelium), by aerosol spray (for
oropharyngeal, buccal, tongue, laryngeal or vocal cord epithelium),
or by other means.
[0096] Certain embodiments encompass where the agent provides
protection against damage by a noxious substance to the epithelium
after a short period of contact with the epithelium. In certain
embodiments the period of contact can be, for example, less than or
equal to 1 hour, less than or equal to 30 minutes, less than or
equal to 15 minutes, less than or equal to 10 minutes, less than or
equal to 5 minutes, less than or equal to 1 minute. In a preferred
embodiment the epithelium is contacted with or exposed to the agent
for about 1 to 5 minutes.
[0097] Tablets and capsules for oral administration are usually
provided in a unit dosage form, and can be prepared by adding
ordinary pharmaceutical carriers such as binders, fillers,
diluents, compressing agents, lubricants, disintegrating agents,
coloring matters, flavoring agents, and moistening agents. Tablets
may be coated according to a well known method, for example, by
using an enteric coating agent. For example, fillers such as
cellulose, mannitol and lactose; disintegrating agents such as
starch, polyvinylpyrrolidone, starch derivatives and sodium
starchglycolate; lubricants such as magnesium stearate; moistening
agents such as sodium laurylsulfate and the like may be used.
[0098] Liquid preparations for oral administration can be provided
in the forms of, for example, aqueous or oily suspensions,
solutions, emulsions, syrups and elixirs, as well as dried
formulations that is re-dissolvable before use by water or a
suitable medium. Those liquid preparations may contain ordinary
additives, for example, suspending agents such as sorbitol, syrups,
methylcellulose, gelatin, hydroxyethylcellulose,
carboxymethylcellulose, aluminum stearate gel and hydrogenated
edible fats; emulsifiers such as lecitin, sorbitan monooleate and
gum arabic; non-aqueous media including edible oils such as almond
oil, rectified coconut oil, oily esters (e.g., esters of glycerin),
propylene glycol and ethyl alcohol; preservatives such as methyl
ester, ethyl ester and propyl ester of p-hydroxybenzoic acid and
sorbic acid; and usual flavoring agents and coloring matters as
required.
[0099] Formulations for oral administration can be manufactured
according to a method well known in the art, for example, by
mixing, filling, compressing and the like. In addition, it is also
possible to disperse the active ingredient in a formulation
containing a large amount of filler by repetitive mixing.
Formulations for parenteral administration are generally provided
as unit dosage form preparations containing the compound as the
active ingredient and a sterilized medium. The solution for
parenteral administration may generally be prepared by dissolving
the compound in a medium, subjecting the resulting solution to
filtration for sterilization, filling the solution in vials or
ampoules, and sealing the vials or ampoules. It is also possible to
freeze the composition and fill the result in vials, and then
eliminate the moisture in vacuo to improve stability. Parenteral
suspensions can be prepared by substantially the same method as
that applied to solutions for parenteral administration; however,
the suspensions can preferably be manufactured by suspending the
active ingredient in a medium, and then subjecting the result to
sterilization by using ethylene oxide or the like. Furthermore,
surface active agents, moistening agents and so forth may also be
added so that a uniform dispersion of the active ingredient can be
obtained.
[0100] Combining two or more active ingredients in single dosage
form results in the possibility of chemical interactions between
the active drug substances. For example, acidic and basic active
ingredients can react with each other and acidic active ingredients
can facilitate the degradation of acid labile substances. Thus, in
certain dosage forms, acidic and basic substances can be physically
separated as two distinct or isolated layers in a compressed
tablet, or in the core and shell of a press-coated tablet.
Additional agents that are compatible with acidic as well as basic
substances, have the flexibility of being placed in either layer.
In certain multiple layer compositions at least one active
ingredient can be enteric-coated. In certain embodiments thereof at
least one active ingredient can be presented in a controlled
release form. In certain embodiments where a combination of three
or more active substances are used, they can be presented as
physically isolated segments of a compressed mutlilayer tablet,
which can be optionally film coated.
[0101] The therapeutic combinations described herein can be
formulated as a tablet or capsule comprising a plurality of beads,
granules, or pellets. All active ingredients including the vitamins
of the combination are formulated into granules or beads or pellets
that are further coated with a protective coat, an enteric coat, or
a film coat to avoid the possible chemical interactions.
Granulation and coating of granules or beads is done using
techniques well known to a person skilled in the art. At least one
active ingredient can present in a controlled release form. Finally
these coated granules or beads are filled into hard gelatin
capsules or compressed to form tablets.
[0102] The therapeutic combinations described herein can be
formulated as a capsule comprising microtablets or minitablets of
all active ingredients. Microtablets of the individual agents can
be prepared using well known pharmaceutical procedures of tablet
making like direct compression, dry granulation or wet granulation.
Individual microtablets can be filled into hard gelatin capsules. A
final dosage form may comprise one or more microtablets of each
individual component. The microtablets may be film coated or
enteric coated.
[0103] The therapeutic combinations described herein can be
formulated as a capsule comprising one or more microtablets and
powder, or one or more microtablets and granules or beads. In order
to avoid interactions between drugs, some active ingredients of a
said combination can be formulated as microtablets and the others
filled into capsules as a powder, granules, or beads. The
microtablets may be film coated or enteric coated. At least one
active ingredient can be presented in controlled release form.
[0104] The therapeutic combinations described herein can be
formulated wherein the active ingredients are distributed in the
inner and outer phase of tablets. In an attempt to divide
chemically incompatible components of proposed combination, few
interacting components are converted in granules or beads using
well known pharmaceutical procedures in prior art. The prepared
granules or beads (inner phase) are then mixed with outer phase
comprising the remaining active ingredients and at least one
pharmaceutically acceptable excipient. The mixture thus comprising
inner and outer phase is compressed into tablets or molded into
tablets. The granules or beads can be controlled release or
immediate release beads or granules, and can further be coated
using an enteric polymer in an aqueous or non-aqueous system, using
methods and materials that are known in the art.
[0105] The therapeutic combinations described herein can be
formulated as single dosage unit comprising suitable buffering
agent. All powdered ingredients of said combination are mixed and a
suitable quantity of one or more buffering agents is added to the
blend to minimize possible interactions.
[0106] The agents described herein, alone or in combination, can be
combined with any pharmaceutically acceptable carrier or medium.
Thus, they can be combined with materials that do not produce an
adverse, allergic or otherwise unwanted reaction when administered
to a patient. The carriers or mediums used can include solvents,
dispersants, coatings, absorption promoting agents, controlled
release agents, and one or more inert excipients (which include
starches, polyols, granulating agents, microcrystalline cellulose,
diluents, lubricants, binders, disintegrating agents, and the
like), etc. If desired, tablet dosages of the disclosed
compositions may be coated by standard aqueous or nonaqueous
techniques. The agents described herein, alone or in combination,
can be formulated using Nanocrystal.RTM. technology (Elan
Corporation, Dublin, Ireland).
[0107] The agents can be a free acid or base, or a
pharmacologically acceptable salt thereof. Solids can be dissolved
or dispersed immediately prior to administration or earlier. In
some circumstances the preparations include a preservative to
prevent the growth of microorganisms. The pharmaceutical forms
suitable for injection can include sterile aqueous or organic
solutions or dispersions which include, e.g., water, an alcohol, an
organic solvent, an oil or other solvent or dispersant (e.g.,
glycerol, propylene glycol, polyethylene glycol, and vegetable
oils). The formulations may contain antioxidants, buffers,
bacteriostats, and solutes that render the formulation isotonic
with the blood of the intended recipient, and aqueous and
non-aqueous sterile suspensions that can include suspending agents,
solubilizers, thickening agents, stabilizers, and preservatives.
Pharmaceutical agents can be sterilized by filter sterilization or
by other suitable means
[0108] Suitable pharmaceutical compositions in accordance with the
invention will generally include an amount of the active
compound(s) with an acceptable pharmaceutical diluent or excipient,
such as a sterile aqueous solution, to give a range of final
concentrations, depending on the intended use. The techniques of
preparation are generally well known in the art, as exemplified by
Remington's Pharmaceutical Sciences, 19th Ed., Mack Publishing
Company, 1995.
[0109] The agent can be in the form of a pharmaceutically
acceptable salt. Such salts are prepared from pharmaceutically
acceptable non-toxic bases including inorganic bases and organic
bases. Examples of salts derived from inorganic bases include
aluminum, ammonium, calcium, copper, ferric, ferrous, lithium,
magnesium, manganic salts, manganous, potassium, sodium, zinc, and
the like. In some embodiments, the salt can be an ammonium,
calcium, magnesium, potassium, or sodium salt. Examples of salts
derived from pharmaceutically acceptable organic non-toxic bases
include salts of primary, secondary, and tertiary amines,
benethamine, N,N'-dibenzylethylenediamine, diethylamine,
2-diethylaminoethanol, 2-dimethylaminoethanol, diethanolamine,
ethanolamine, ethylenediamine, N-ethylmorpholine,
N-ethylpiperidine, epolamine, glucamine, glucosamine, histidine,
hydrabamine, isopropylamine, lysine, methylglucamine, meglumine,
morpholine, piperazine, piperidine, polyamine resins, procaine,
purines, theobromine, triethylamine, trimethylamine,
tripropylamine, and trolamine, tromethamine. Examples of other
salts include tris, arecoline, arginine, barium, betaine, bismuth,
chloroprocaine, choline, clemizole, deanol, imidazole, and
morpholineethanol.
[0110] The agents of the invention can be administered orally,
e.g., as a tablet or cachet containing a predetermined amount of
the active ingredient, pellet, gel, paste, syrup, bolus, electuary,
slurry, capsule; powder; granules; as a solution or a suspension in
an aqueous liquid or a non-aqueous liquid; as an oil-in-water
liquid emulsion or a water-in-oil liquid emulsion, via a liposomal
formulation (see, e.g., EP736299) or in some other form. Orally
administered compositions can include binders, lubricants, inert
diluents, lubricating, surface active or dispersing agents,
flavoring agents, and humectants. Orally administered formulations
such as tablets may optionally be coated or scored and may be
formulated so as to provide sustained, delayed or controlled
release of the active ingredient therein.
Gastric-Retention Vehicles
[0111] A traditional oral sustained-release formulation releases
most of the drug at the colon. Thus, clinically acceptable
sustained release dosage forms prepared with conventional
technology may not be successful where a particular drug has an
absorption window in a particular region of the gastrointestinal
tract, such as the duodenum and upper jejunem segments. In such
cases, a gastroretentive drug delivery system can be employed to
help retain the active ingredient in the stomach, thereby assisting
in and improving the sustained delivery of the drug.
[0112] Several approaches are currently used to prolong gastric
retention time. These include floating drug delivery systems, also
known as hydrodynamically balanced systems, swelling and expanding
systems, polymeric bioadhesive systems, modified-shape systems,
high-density systems, and other delayed gastric emptying systems.
For example, Dave et al. AAPS PharmSciTech 2004; 5(2), 1-6, report
on a gastroretentive drug delivery system of ranitidine
hydrochloride using the principles of buoyant preparation, wherein
guar gum, xanthan gum, and hydroxypropyl methylcellulose were
evaluated for gel-forming properties, sodium bicarbonate was used
as a gas-generating agent, and the effects of citric acid and
stearic acid on drug release profile and floating properties were
investigated. Similarly, Narendra et al. AAPS PharmSciTech 2006,
7(2), E1-7, reports on the development of an optimized gastric
floating drug delivery system containing metoprolol tartrate as a
model drug, wherein the dosage form was prepared as a bilayer
tablet comprising a drug-loading layer and a floating layer in a
suitable ratio to provide a bulk density lower than that of gastric
fluids to remain buoyant on the stomach contents.
[0113] Other variations of gastric-retention vehicle compositions
are known to those skilled in the art and are suitable for use with
the compositions and methods described in detail and disclosed
herein. For example, in certain embodiments, the present invention
provides methods of making a gastro-retentive dosage form of any of
the compositions described herein, wherein said method comprises
(a) forming a tablet comprising any composition described herein, a
binder and a pharmaceutically-acceptable gas-generating agent, (b)
surrounding the tablet with an expandable, hydrophilic,
water-permeable and substantially gas-impermeable, membrane, and
(c) sealing the membrane to retard the escape of gas from within
the sealed membrane. A further optional step comprises (d)
encapulating the membrane-sealed tablet within a covering that
disintegrates without delay upon contact with gastric fluid.
[0114] Active
[0115] The active ingredient in the gastro-retentive dosage forms
of the present invention includes any of the compositions described
in detail and disclosed herein in an amount as contemplated and
described below.
[0116] The tablet component contains the active ingredient (e.g.,
at least one bile acid sequestrant, alone or in combination with at
least one proton pump inhibitor and/or optionally one or more other
agents) in a therapeutically effective amount. Typically, the
active ingredient(s) is present in an amount from between 10% to
about 50% of the total tablet weight, preferably between about 15%
and about 40%. Other therapeutically effective dosages can be
readily determined by one of skill in the pharmaceutical or medical
arts.
[0117] Binder
[0118] The tablet component of the gastro-retentive dosage form
comprises the active ingredient (for example, at least one bile
acid sequestrant or combinations of at least one bile acid
sequestrant and at least one proton pump inhibitor), a
gas-generating agent and a binder. Binders (also called wetting
agents) are agents used to improve the cohesiveness of the tablet
formulation, ensuring that the tablet will remain intact after
formation. Suitable binders for use in the gastric-retention
vehicle for use with the present invention include but are not
limited to poloxamers, polyethylene glycols (e.g., PEG 3350),
polyethylene glycol fatty acid esters (e.g., Myrj), glyceryl
palmitostearate (e.g. Precirol AT05), polyoxyethylene alkyl ethers,
glyceryl behenate (e.g., Compritol 888), stearoyl
macrogol-32-glyceride (e.g., Gelucire), polyoxyethylene castor oil
derivatives, polyoxyethylene sorbitan fatty acid derivatives,
polyoxyethylene stearates, polyoxyethylene-polyoxypropylene
copolymers (e.g. Lutrol or Pluronics), starches, gelatin, sugars
such as lactose, sucrose, glucose and molasses, natural and
synthetic gums such as acacia, sodium alginate,
carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone,
ethyl cellulose and waxes. Suitable binders also include Myrj52
(particularly Myrj52P or Myrj52FL), Lutrol F68, Compritol 888,
Gelucire 50/13, PEG 3350, Precirol ATOS methylcellulose and
polyvinyl pyrrolidone.
[0119] The binder is present in the tablet component in an amount
effective to provide cohesion to the final tablet form. The
appropriate amount of binder can be readily determined by one of
ordinary skill in the pharmaceutical arts and will depend, inter
alia, upon the particular binder used and the method of preparation
of the tablet. The binder may be present in the tablet in an amount
from between about 8% to about 15% of the total tablet weight.
[0120] Gas-Generating Agent
[0121] A gas-generating agent may be included in the tablet
component to generate the carbon dioxide gas that results in the
expansion of the membrane component upon contact with gastric
juice. Suitable gas-generating agents are, for example, solids that
liberate this gas itself, for example under the action of body
fluid or the hydrogen ions present therein. Such gas-generating
agents are, for example, those capable of releasing carbon dioxide
and include, but are not limited to, pharmaceutically acceptable
mono- and di-basic salts of carbonic acid, for example alkali metal
hydrogen carbonates or alkali metal carbonates, alkaline earth
metal carbonates or ammonium carbonate.
[0122] Such mono- or di-basic salts of carbonic acid are especially
sodium hydrogen carbonate (sodium bicarbonate) or sodium carbonate,
potassium carbonate, calcium carbonate, magnesium carbonate, sodium
glycine carbonate, or mixtures thereof. In order to increase the
evolution of carbon dioxide, there may be added to the mentioned
carbonates the acid component customarily used in effervescent
mixtures, for example sodium dihydrogen phosphate or disodium
hydrogen phosphate, sodium tartrate, sodium ascorbate or sodium
citrate. Also suitable are yeasts which are likewise capable of
generating carbon dioxide gas. When yeasts, for example baker's
yeast, are used, the necessary nutrients, for example glucose, are
added to the formulation. In certain embodiments, the
gas-generating agent will be sodium hydrogen carbonate.
[0123] The gas-generating agent may be present in the tablet
component in an amount between about 30% and about 82% of the total
tablet weight. In certain embodiments, the gas-generating agent is
present at about 40% to about 82% of the total tablet weight.
[0124] Other Agents
[0125] In addition to the active ingredient, the binder and the
gas-generating agent, the tablet component may also include one or
more of diluents, glidants, lubricants, acidulants, swelling
agents, surfactants and other pharmaceutically acceptable
excipients. A diluent is a substance added to increase the bulk of
a mixture to make a tablet a practical size for granulation,
compression or molding when only a small amount of active is
present. Suitable diluents include lactose, cellulose, dry starch,
powdered sugar, dicalcium phosphate, calcium sulfate, sodium
chloride, kaolin, mannitol, sorbitol, sucrose, inositol. In certain
embodiments, the diluent is lactose, sorbitol, mannitol, cellulose
or starch. A glidant (or flow-enhancing agent) is a substance that
improves the flow characteristics of a powder mixture. Commonly
used glidants include colloidal silicon dioxide, magnesium tri
silicate, powdered cellulose, starch, tribasic calcium phosphate
and talc. Glidants useful in this invention include these commonly
used glidants. In certain embodiments, the glidant is Aerosil 200,
colloidal silicon dioxide. A lubricant is a substance that has a
number of functions in the preparation of the tablet component of
this invention, including preventing the adhesion of the tablet
material to the surface of the dies and punches, reducing
interparticle friction, facilitating the ejection of the tablet
from the die cavity and in some instances, improving the rate of
flow of the tablet granulation. Commonly used lubricants include
talc, magnesium stearate, calcium stearate, zinc stearate, stearic
acid, glyceryl monostearate, glyceryl palmitostearate, hydrogenated
vegetable oils, hydrogenated castor oil, light mineral oil, sodium
benzoate, sodium stearyl fumarate and polyethylene glycol (PEG).
Any of the commonly used lubricants are suitable for use in the
present invention. In one embodiment, magnesium stearate is used as
a lubricant. An acidulant may be added to increase the release of
carbon dioxide from this sodium hydrogen carbonate. Commonly used
acidulants include citric acid, fumaric acid, malic acid and
tartaric acid. It will be apparent from the foregoing that a single
substance may serve more than one of the purposes described
above.
[0126] Swelling Agents
[0127] In addition to the afore-mentioned gas-generating agents, it
is also possible for intensifying the action of the agent to use
pharmaceutically acceptable hydrophilic swelling agents, for
example partially etherified cellulose derivatives, starches,
water-soluble, aliphatic or cyclic poly-N-vinylamides, polyvinyl
alcohols, polyacrylates, polymethacrylates, polyethylene glycols or
mixtures of these auxiliaries. In certain embodiments, the
hydrophilic swelling agent may also serve as a binder.
[0128] Hydrophilic, partially etherified cellulose derivatives are,
for example, lower alkyl ethers of cellulose having an average
degree of molar substitution (MS) of more than 1 and less than 3
and an average degree of polymerisation of approximately
100-5000.
[0129] The degree of substitution is a measure of the substitution
of the hydroxy groups by lower alkoxy groups per glucose unit. The
average degree of molar substitution (MS) is a mean value and
indicates the number of lower alkoxy groups per glucose unit in the
polymer.
[0130] The average degree of polymerisation (DP) is likewise a mean
value and indicates the average number of glucose units in the
cellulose polymer.
[0131] Lower alkyl ethers of cellulose are, for example, cellulose
derivatives that are substituted at the hydroxymethyl group
(primary hydroxy group) of the glucose unit forming the cellulose
chains and optionally at the second and third secondary hydroxy
group by C.sub.1-C.sub.4 alkyl groups, especially methyl or ethyl,
or by substituted C.sub.1-C.sub.4 alkyl groups, for example
2-hydroxyethyl, 3-hydroxy-n-propyl, carboxymethyl or
2-carboxyethyl.
[0132] Suitable lower alkyl ethers of cellulose include
methylcellulose, ethylcellulose, methylhydroxyethylcellulose,
methylhydroxypropylcellulose, ethylhydroxyethylcellulose,
hydroxyethylcellulose, hydroxypropylcellulose,
carboxymethylcellulose (in salt form, for example sodium salt form)
or methylcarboxymethylcellulose (likewise in salt form, for example
sodium salt form).
[0133] A starch suitable for use as hydrophilic swelling agent is,
for example, a mixture of approximately 15-20% amylose (molar mass
approximately 50,000 to 200,000) and 80-85% amylopectin (molar mass
approximately 100,000 to 1,000,000), for example rice, wheat or
potato starch, and also starch derivatives, such as partially
synthetic amylopectin, for example sodium carboxymethylamylopectin,
and alginates of the alginic acid type.
[0134] Water-soluble, aliphatic or cyclic poly-N-vinylamides
include, for example, poly-N-vinyl-methylacetamide,
poly-N-vinylethylacetamide, poly-N-vinylmethylpropionamide,
poly-N-vinylethylpropionamide, poly-N-vinylmethylisobutyramide,
poly-N-vinyl-2-pyrrolidone, poly-N-vinyl-2-piperidone,
poly-N-vinyl-.epsilon.-caprolactam,
poly-N-vinyl-5-methyl-2-pyrrolidone or
poly-N-vinyl-3-methyl-2-pyrrolidone, especially
poly-N-vinylpyrrolidone having a mean molar mass of approximately
10,000-360,000, for example the polyvinylpyrrolidone obtainable
under the trade mark Kollidon.RTM. (BASF).
[0135] Suitable polyvinyl alcohols have a mean molar mass of
approximately 15,000 to 250,000 and a degree of hydrolysis of
approximately 70-99%. In certain embodiments, the polyvinyl
alcohols have a degree of hydrolysis of approximately 70-88%
(partially hydrolysed polyvinyl alcohol), for example the polyvinyl
alcohol obtainable under the trade name Mowiol.RTM. (Hoechst)
denoted by MOWIOL 3-83, 4-80, 4-88, 5-88 or 8-88.
[0136] Hydrophilic polyacrylates that can be used as swelling
agents have a mean molecular weight of approximately
8.6.times.10.sup.5 to 1.0.times.10.sup.6. The polyacrylic acid
chains carry a greater or smaller number of short side chains and
so the individual commercial forms differ in this respect, as well
as in having different molecular weights. In some embodiments,
neutralised (for example with dilute aqueous sodium hydroxide
solution) polyacrylic acid derivatives of the commercial form
Carbopol.RTM. (Goodrich), for example CARBOPOL 934 P or CARBOPOL
940, are used.
[0137] Suitable polymethacrylates are likewise swellable and have a
mean molecular weight of more than 1.0.times.10.sup.6. Commercial
forms that can be used include the polymers of methacrylic acid and
methacrylic acid esters of the Eudragit.RTM. type, for example
EUDRA-GIT L or EUDRAGIT S (Rohm GmbH).
[0138] Suitable polyethylene glycols have an average molecular
weight of approximately 4000 to 6000. Pharmaceutical-quality
commercial forms are preferred, for example polyethylene glycol
such as Lutrol.RTM. (BASF), Polydiol.RTM., Polywachs.RTM. (Huls),
Polyglykol.RTM., Lanogen.RTM. (Hoechst), Carbowax.RTM. (Union
Carbide), Plurocol.RTM. (Wyandotte) or Tetronic.RTM.
(Kuhlmann).
[0139] Suitable hydrophilic swelling agents are also homopolymers,
such as polyhydroxyalkyl methacrylate having a molecular weight
from 5,000 to 5,000,000 anionic or cationic hydrogels, mixtures of
agar and carboxymethylcellulose, swellable agents consisting of
methylcellulose in admixture with weakly cross-linked agar, or
water-swellable polymers that can be produced by dispersion of a
finely particulate copolymer of maleic acid anhydride and styrene,
or tragacanth, gelatine or swellable ion exchange resins.
[0140] Swellable ion exchangers are, for example, copolymer resins
having acidic groups, for example, sulfonic acid groups or salt
forms thereof based on styrene-divinylbenzene. Such copolymer
resins consist of cross-linked styrene polymers which are obtained
by copolymerization of styrene with divinylbenzene as cross-linking
agent. Customary derivisation reactions, for example sulfonation
reactions, are used to incorporate acidic groups, such as sulfo
groups, into the structure. The preparation and the properties of
these resins are known. Reference is made to the article in
Ullmanns Enzyklopdie der Technischen Chemie, 4th Edition, Vol. 13,
pp. 279 ff., and to Kirk-Othmer, Encyclopaedia of Chemical
Technology, J. Wiley, Vol. 13, pp. 678 ff., and to the numerous
literature references cited therein.
[0141] Preferred ion exchange resins are those having quaternary
ammonium groups or sulfonic acid groups based on
styrenedivinylbenzene which are commercially available and are
acceptable for use in pharmaceutical formulations, for example
resins marketed by the firm Rohm and Haas under the trade mark
Amberlite.RTM. IRP-69.
[0142] Surfactants
[0143] The tablet component can also contain the customary
pharmaceutical formulation adjuncts that are used at present for
the manufacture of oral dosage forms, such as tablets, for example
surface-active substances, for example so-called surfactants, for
example anionic surfactants of the alkyl sulfate type, for example
sodium, potassium or magnesium n-dodecyl sulfate, n-tetradecyl
sulfate, n-hexadecyl sulfate or n-octadecyl sulfate, alkyl ether
sulfate, for example sodium, potassium or magnesium
n-dodecyloxyethyl sulfate, n-tetradecyloxyethyl sulfate,
n-hexadecyloxyethyl sulfate or n-octadecyloxyethyl sulfate, or
alkanesulfonate, for example sodium, potassium or magnesium
n-dodecanesulfonate, n-tetradecanesulfonate, n-hexadecanesulfonate
or n-octadecanesulfonate.
[0144] Suitable surfactants are also nonionic surfactants of the
fatty acid/polyhydroxy alcohol ester type, such as orbitan
monolaurate, monooleate, monostearate or monopalmitate, sorbitan
tristearate or trioleate, polyoxyethylene adducts of fatty
acid/polyhydroxy alcohol esters, such as polyoxyethylene sorbitan
monolaurate, monooleate, monostearate, monopalmitate, tristearate
or trioleate, polyethylene glycol/fatty acid esters, such as
polyoxyethylene stearate, polyethylene glycol 400 stearate or
polyethylene glycol 2000 stearate, especially ethylene
oxide/propylene oxide block copolymers of the Pluronics.RTM. (BWC)
or Synperonic.RTM. (ICI) type, myristates and their condensation
products, or ethylene oxide homopolymers having a degree of
polymerisation of approximately 2,000 to 100,000, which are known,
for example, under the trade name Polyox.RTM. (Union Carbide).
[0145] Expandable Membrane
[0146] The hydrophilic membrane, which is expandable at the site of
use and is permeable to body fluid, consists of a plastic or
wax-like, pharmaceutically acceptable polymeric material that is
substantially gas-impermeable to the gas generated by the
gas-generating agent. By "substantially gas-impermeable" is meant
that the flow of gas through the membrane is impeded sufficiently
to allow expansion of the membrane sachet or pouch upon the
generation of gas from the gas-generating agent contained in the
tablet component for a suitable period of time. Because of its
hydrophilic properties, the membrane can absorb body fluid, such as
gastric fluid, and can effect retarded and continuous release of
controlled amounts of the active ingredients contained in the
tablet component by means of diffusion or optionally by the use of
osmosis.
[0147] Suitable plastic or wax-like polymeric materials for the
expandable hydrophilic membrane include for example hydrophilic
foils, for example foils of cellulose ethers, such as methyl- or
ethyl-cellulose, hydroxypropylcellulose, methyl- or
ethyl-hydroxyethylcellulose, methyl- or
ethyl-hydroxypropylcellulose carboxymethylcellulose, polyvinyl
alcohol, polyvinyl acetate, polyvinylpyrrolidone,
polyacrylonitrile, mixtures of polyvinylpyrrolidone with polyvinyl
alcohol, resins based on phthalic acid anhydride/polyhydroxy
alcohol, urethanes, polyamides, shellac, etc.
[0148] In certain embodiments, polyvinyl alcohols having a degree
of hydrolysis of more than 92% (fully hydrolysed polyvinyl
alcohol), especially more than 97%, for example MOWIOL of the 98
series, for example MOWIOL 4-98, 10-98, 20-98, 28-99, 56-98 and
66-100, PVAU228-08 are used. In other embodiments, MOWIOL 28-99 and
PVAU228-08 are utilized.
[0149] To these materials it is possible to add further adjuncts,
for example plasticisers, which improve the elasticity of the
membrane, for example glycerol, polyethylene glycol/fatty acid
esters, such as polyethylene glycol 400 stearate or polyethylene
glycol 2000 stearate, triethyl citrate, diethyl phthalate, diethyl
sebacate, and the like. The amount of plasticiser added is
approximately from 0.01 to 60% by weight, based on the total weight
of the dosage form. Glycerol at 10-30% w/w may be used as the
plasticizer, for example, at 20%.
[0150] In one embodiment, the expandable membrane is produced by
preparing a homogeneous mixture of polyvinyl alcohol and additives,
such as plasticisers, for example glycerol and/or polyethylene
glycol 400 stearate, by dissolution in water, which is optionally
heated, and evaporation to form layers of suitable thickness, for
example 100 mm, or by allowing a solution of polyvinyl alcohol in
water (without additives) to evaporate. The film or the foil which
is obtainable after evaporation of an aqueous solution of polyvinyl
alcohol, especially polyvinyl alcohol having a degree of hydrolysis
of more than 97%, and polyethylene glycol/fatty acid ester, for
example polyethylene glycol 400 stearate or polyethylene glycol
2000 stearate, optionally with the addition of plasticisers, such
as glycerol, is distinguished by a high degree of extensibility. A
film-like residue which can be obtained after evaporation of an
aqueous solution containing approximately 40-85% polyvinyl alcohol,
0-40% polyethylene glycol stearate and 10-30% glycerol has
particularly advantageous properties. This film is distinguished by
particularly good extensibility. This film can be easily cut and
formed into pouches or sachets to accommodate individual tablet
components or used as a sheet to fold around the tablet component
or several sheets of membrane film can be used to sandwich the
tablet components.
[0151] Optional Covering
[0152] In certain embodiments, the gastro-retentive vehicle for use
in accordance with the invention can be provided with a covering
which surrounds or contains the tablet component and the membrane
component and which disintegrates without delay under the action of
body fluid at the site of use and which consists of a film coating
or, preferably, a covering in capsule form.
[0153] Suitable film coatings delay the release of active
ingredient only slightly or not at all. Water-soluble film coatings
from approximately 20 .mu.m to approximately 150 .mu.m in thickness
are preferred. Suitable film coating materials are especially
hydrophilic cellulose derivatives, such as cellulose ethers, for
example methylcellulose, hydroxypropylcellulose or especially
hydroxypropylmethylcellulose, mixtures of polyvinylpyrrolidone or
of a copolymer of polyvinylpyrrolidone and polyvinyl acetate with
hydroxypropylmethylcellulose, mixtures of shellac with
hydroxypropylmethylcellulose, polyvinyl acetate or copolymers
thereof with polyvinylpyrrolidone, or mixtures of water-soluble
cellulose derivatives, such as hydroxypropylmethylcellulose-, and
water-insoluble ethylcellulose. These coating agents can, if
desired, be used in admixture with other adjuncts, such as talc,
wetting agents, for example polysorbates (for example to facilitate
application), or pigments (for example for identification
purposes). Depending upon the solubility of the components, these
coatings are applied in aqueous solution or in organic solution
(for example solutions of shellac or ethylcellulose in organic
solvents). It is also possible to use mixtures of acrylates that
are water-insoluble per se, for example the copolymer of ethyl
acrylate and methyl methacrylate, which are used in aqueous
dispersion, with water-soluble adjuncts, for example lactose,
polyvinylpyrrolidone, polyethylene glycol or
hydroxypropylmethylcellulose-.
[0154] Instead of using a film-like coating, the gastro-retentive
vehicles for use in accordance with the invention can be provided
with a covering in capsule form. Hard gelatin capsules having high
watersolubility and/or swellability are preferred. Size 000, Size
00 and Size 0 dry-fill capsules such as by Capsugel are preferred,
in order to accommodate the membrane enclosed tablets.
[0155] When present, the covering is preferably a dry-fill capsule,
more preferably a hard gelatin dry-fill capsule.
[0156] Preparation of the Gastro-Retentive Vehicles
[0157] In an aspect, the present invention provides a method of
making a gastro-retentive dosage form of the compositions described
in detail and disclosed herein, which method comprises: forming a
tablet comprising any of the compositions disclosed herein, a
binder and a pharmaceutically-acceptable gas-generating agent,
surrounding the tablet with an expandable, hydrophilic,
water-permeable and substantially gas-impermeable membrane, and
sealing the membrane to retard the escape of gas from within the
sealed membrane. Optionally, the method comprises the additional
step of encapsulating the sealed membrane within a covering that
disintegrates without delay upon contact with gastric fluid.
[0158] As described above, the tablet component can be formed using
any convenient tabletting method. Such methods are well known in
the art and are described, for example, in Remington: the Science
and Practice of Pharmacy 19th Ed. 1995 Mack Publishing Co. Easton
Pa.
[0159] In one embodiment of the gastro-retentive dosage form of the
present invention, the tablet component will be surrounded by the
expandable membrane component. The membrane surrounds the tablet on
all sides and is sealed to retard the escape of gas generated by
the gas-generating agent contained in the tablet. This surrounding
can be accomplished in various ways. The membrane may be a
preformed sachet or pouch that contains an opening large enough for
insertion of the tablet component. After insertion of the tablet,
the opening is sealed by appropriate means, for example heat and/or
pressure. Alternatively, the membrane may be formed around the
tablet, for example as a coating on the tablet that completely
surrounds the tablet, or may be formed by sandwiching the tablet
component between two or more separate layers of membrane material,
or one membrane layer folded over the tablet, and sealing the
membrane layers together around the tablet by heat and/or pressure.
Typically, the membrane pouch surrounding the tablet component will
be as small as possible consistent with the need to accommodate the
tablet component and provide for sufficient expansion of the dosage
form in the stomach.
[0160] As mentioned, the hydrophilic membrane is typically prepared
in the form of a sachet or pouch into which the tablet component
can be inserted. Such a pouch or sachet is readily prepared from
the membrane film prepared as described herein. After insertion of
the tablet, the pouch can be sealed around the tablet to retard the
escape of gas generated by the gas-generating agent in the tablet
component. The sachet or pouch can be any convenient shape,
typically will be rectangular or circular. Typically, the
uninflated membrane sachet or pouch is about 20-25 mm in the
longest dimension and may be shorter, depending on the size of the
tablet component that must be accommodated. In some embodiments,
the membrane film will not be preformed into pouches but will be
used as a film layer to surround the tablet component, either by
sandwiching the tablet between two (or more) membrane layers or by
folding a single layer over the tablet. The membrane layers will be
sealed on all sides surrounding the tablet and cut along the seal
to produce the dosage form. Multiple dosage forms may be produced
simultaneously in this way by using a membrane layer large enough
to accommodate multiple tablets, sealing the membrane layers
between the tablets and cutting at the sealed membrane to produce
the dosage forms.
[0161] It is also possible for the tablet component to be
surrounded not by one but by several coverings of expansible
permeable material. With such a multi-layered arrangement, it is
also possible for a formulation of the compositions disclosed
herein, or constituents of the formulation, for example the
gas-generating agent, such as sodium hydrogen carbonate, to be
located between the individual layers. With a multi-layered
arrangement it is possible to achieve an even longer dwell time of
the dosage form at the site of action, for example in the stomach.
In addition, the expansible membrane (b) may itself, contain
physiologically active substances.
[0162] In a one form of the process, the expandable membrane
surrounding tablet component is produced first, for example by
preparing a homogeneous mixture of polyvinyl alcohol and additives,
such as plasticisers, for example glycerol and/or polyethylene
glycol 400 stearate, by dissolution in water, which is optionally
heated, and evaporation to form layers of suitable thickness, for
example 100 mm, or by allowing a solution of polyvinyl alcohol in
water (without additives) to evaporate. The layers are cut into
strips of a suitable size and the active ingredient formulation
consisting of the tablet component is applied. This can be effected
for example, by filling the still open sachet, which is then closed
completely, for example by sealing, for example with heat and/or
pressure. The sealed sachets can then be filled into dry-fill
capsules.
[0163] The gastro-retentive dosage form according to the invention
can be of various shapes and may be, for example, round, oval,
oblong, tubular and so on, and may be of various sizes depending
upon the size and shape of the tablet component. In addition, the
dosage form may be transparent, colourless or coloured in order to
impart to the product an individual appearance and the ability to
be immediately recognised.
[0164] In some embodiments, the gastro-retentive dosage form can be
prepared using microparticulates or nanoparticulates comprising the
active (i.e., bile acid sequestrant or bile acid sequestrant:proton
pump inhibitor combinations) in lieu of a tablet. The
microparticulates or nanoparticulates will comprise the active
ingredient, a binder and a gas-generating agent, optionally other
agents as described herein, and other optional components as
described for the tablets. The microparticulates or
nanoparticulates are prepared using, for example, the granulation
techniques described herein or other well known methods for
preparing microparticulates and nanoparticulates.
[0165] Other gastro-retentive forms and methods of making and using
the same are known to those skilled in the art and are also
suitable for use in accordance with the compositions described in
detail and disclosed herein, and include, for example, any of those
described and disclosed in U.S. Pat. Nos. 4,996,058; 6,881,420;
6,776,999; 6,723,340; 6,685,962; 6,548,083; 5,972,389; 4,851,232;
4,735,804 and U.S. Published Application Nos. 20070269512;
20070196396; 20070190140; 20060013876; 20050202090; 20040180086;
20030104053; and 20030021845, each of which are incorporated herein
by reference in its entirety.
Dosing and Regimen
[0166] Doses of the aforementioned compound as the active
ingredient can be suitably decided depending on the purpose of
administration, i.e., therapeutic or preventive treatment, nature
of a disease to be treated or prevented, conditions, body weight,
age, sexuality and the like of a patient. In the method for
administering the pharmaceutical preparation according to the
present disclosure, the proton pump inhibitor and/or other optional
agent may be administered simultaneously with the bile acid
sequestrant or the agent(s) may be sequentially administered in an
optional order. The practically desirable method and sequence for
administration varies depending on the purpose of administration,
i.e., therapeutic or preventive treatment, nature of a disease to
be treated or prevented, conditions, body weight, age, sexuality
and the like of a patient. The optimum method and sequence for
administration of the compounds described in detail herein under
preset given conditions may be suitably selected by those skilled
in the art with the aid of the routine technique and the
information contained in the present specification.
[0167] Typically, an amount of about 2 g to 24 g of a bile acid
sequestrant per day for an adult may be administered orally.
Alternatively, an amount of about 10 mg to 80 mg of a proton pump
inhibitor and about 2 g to 24 g of a bile acid sequestrant per day
for an adult may be administered orally. Such doses may be
desirably administered once a day to several times a day as divided
portions. For example, the compositions of the present disclosure
may be administered at least 1.times., 2.times., 3.times.,
4.times., 5.times., 6.times., 8.times., 10.times. or 20.times.. A
preferred embodiment includes where the composition described
herein is administered at least once a day for a period of days,
weeks, months or years. The agent may be administered at least
once, twice, three, or four times daily. Depending upon the desired
therapeutic action, patient response and other factors, the dosage
form may be administered between meals, during meals, prior to a
meal (i.e., within 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60
minutes, 2 hours, 4 hours, 8 hours, or 12 hours prior to eating) or
after a meal (i.e., within 5, 10, 15, 20, 25, 30, 35, 40, 45, 50,
55, or 60 minutes, 2 hours, 4, hours, 8 hours, or 12 hours
following a meal).
[0168] A dosage unit (e.g. an oral dosage unit) can include from,
for example, at least about or less than about 1 g to at least
about or less than about 30 g (e.g. at least about or less than
about 1 g, at least about or less than about 2 g, at least about or
less than about 3 g, at least about or less than about 4 g, at
least about or less than about 5 g, at least about or less than
about 6 g, at least about or less than about 7 g, at least about or
less than about 8 g, at least about or less than about 9 g, at
least about or less than about 10 g, at least about or less than
about 11 g, at least about or less than about 12 g, at least about
or less than about 13 g, at least about or less than about 14 g, at
least about or less than about 15 g, at least about or less than
about 16 g, at least about or less than about 17 g, at least about
or less than about 18 g, at least about or less than about 19 g, at
least about or less than about 20 g, at least about or less than
about 21 g, at least about or less than about 22 g, at least about
or less than about 23 g, at least about or less than about 24 g, at
least about or less than about 25 g, at least about or less than
about 26 g, at least about or less than about 27 g, at least about
or less than about 28 g, at least about or less than about 29 g, at
least about or less than about 30 g) of a bile acid sequestrant
(e.g., cholestyramine, colesevelam, colesevelam-HCl,
ursodeoxycholic acid). A dosage unit (e.g. an oral dosage unit) can
include from, for example, at least about or less than about 1 to
at least about or less than about 200 mg, at least about or less
than about 5 mg to at least about or less than about 100 mg, at
least about or less than about 10 to at least about or less than
about 120 mg, at least about or less than about 20 to at least
about or less than about 100 mg, at least about or less than about
40 mg to at least about or less than about 100 mg, at least about
or less than about 5 to at least about or less than about 80 mg, at
least about or less than about 10 to at least about or less than
about 40 mg, at least about or less than about 10 mg to at least
about or less than about 60 mg, at least about or less than about 1
mg, at least about or less than about 2 mg, at least about or less
than about 3 mg, at least about or less than about 4 mg, at least
about or less than about 5 mg, at least about or less than about 10
mg, at least about or less than about 15 mg, at least about or less
than about 20 mg, at least about or less than about 25 mg, at least
about or less than about 30 mg, at least about or less than about,
at least about or less than about 35 mg, at least about or less
than about 40 mg, at least about or less than about 45 mg, at least
about or less than about 50 mg, at least about or less than about
55 mg, at least about or less than about 60 mg, at least about or
less than about 65 mg, at least about or less than about 70 mg, at
least about or less than about 75 mg, at least about or less than
about 80 mg, at least about or less than about 85 mg, at least
about or less than about 90 mg, at least about or less than about
95 mg, at least about or less than about 100 mg, at least about or
less than about 105 mg, at least about or less than about 110 mg,
at least about or less than about 115 mg, at least about or less
than about 120 mg of a proton pump inhibitor (e.g. omeprazole,
esomeprazole, lansoprazole, pantoprazole, rabeprazole,
tenatoprazole, leminoprazole, dontoprazole, and ransoprazole) and
from at least about or less than about 1 g to at least about or
less than about 30 g (e.g. at least about or less than about 1 g,
at least about or less than about 2 g, at least about or less than
about 3 g, at least about or less than about 4 g, at least about or
less than about 5 g, at least about or less than about 6 g, at
least about or less than about 7 g, at least about or less than
about 8 g, at least about or less than about 9 g, at least about or
less than about 10 g, at least about or less than about 11 g, at
least about or less than about 12 g, at least about or less than
about 13 g, at least about or less than about 14 g, at least about
or less than about 15 g, at least about or less than about 16 g, at
least about or less than about 17 g, at least about or less than
about 18 g, at least about or less than about 19 g, at least about
or less than about 20 g, at least about or less than about 21 g, at
least about or less than about 22 g, at least about or less than
about 23 g, at least about or less than about 24 g, at least about
or less than about 25 g, at least about or less than about 26 g, at
least about or less than about 27 g, at least about or less than
about 28 g, at least about or less than about 29 g, at least about
or less than about 30 g) of a bile acid sequestrant (e.g.,
cholestyramine, colesevelam, colesevelam-HCl, ursodeoxycholic
acid). A dosage unit (e.g. an oral dosage unit) can include from,
for example, at least about or less than about 0.2 g to at least
about or less than about 6 g (e.g. at least about or less than
about 0.2 g, at least about or less than about 0.4 g, at least
about or less than about 0.6 g, at least about or less than about
0.8 g, at least about or less than about 1 g, at least about or
less than about 1.2 g, at least about or less than about 1.4 g, at
least about or less than about 1.6 g, at least about or less than
about 1.8 g, at least about or less than about 2 g, at least about
or less than about 2.2 g, at least about or less than about 2.4 g,
at least about or less than about 2.6 g, at least about or less
than about 2.8 g, at least about or less than about 3 g, at least
about or less than about 3.2 g, at least about or less than about
3.4 g, at least about or less than about 3.6 g, at least about or
less than about 3.8 g, at least about or less than about 4 g, at
least about or less than about 4.2 g, at least about or less than
about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, at least about or less than about 6
g) of a bile acid sequestrant (e.g., cholestyramine, colesevelam,
colesevelam-HCl, ursodeoxycholic acid). A dosage unit (e.g. an oral
dosage unit) can include from, for example, at least about or less
than about 1 to at least about or less than about 200 mg, at least
about or less than about 5 mg to at least about or less than about
100 mg, at least about or less than about 10 to at least about or
less than about 120 mg, at least about or less than about 20 to at
least about or less than about 100 mg, at least about or less than
about 40 mg to at least about or less than about 100 mg, at least
about or less than about 5 to at least about or less than about 80
mg, at least about or less than about 10 to at least about or less
than about 40 mg, at least about or less than about 10 mg to at
least about or less than about 60 mg, at least about or less than
about 1 mg, at least about or less than about 2 mg, at least about
or less than about 3 mg, at least about or less than about 4 mg, at
least about or less than about 5 mg, at least about or less than
about 10 mg, at least about or less than about 15 mg, at least
about or less than about 20 mg, at least about or less than about
25 mg, at least about or less than about 30 mg, at least about or
less than about 35 mg, at least about or less than about 35 mg, at
least about or less than about 40 mg, at least about or less than
about 45 mg, at least about or less than about 50 mg, at least
about or less than about 55 mg, at least about or less than about
60 mg, at least about or less than about 65 mg, at least about or
less than about 70 mg, at least about or less than about 75 mg, at
least about or less than about 80 mg, at least about or less than
about 85 mg, at least about or less than about 90 mg, at least
about or less than about 95 mg, at least about or less than about
100 mg, at least about or less than about 105 mg, at least about or
less than about 110 mg, at least about or less than about 115 mg,
at least about or less than about 120 mg of a proton pump inhibitor
(e.g. omeprazole, esomeprazole, lansoprazole, pantoprazole,
rabeprazole, tenatoprazole, leminoprazole, dontoprazole, and
ransoprazole) and from at least about or less than about 0.2 g to
at least about or less than about 6 g (e.g. at least about or less
than about 0.2 g, at least about or less than about 0.4 g, at least
about or less than about 0.6 g, at least about or less than about
0.8 g, at least about or less than about 1 g, at least about or
less than about 1.2 g, at least about or less than about 1.4 g, at
least about or less than about 1.6 g, at least about or less than
about 1.8 g, at least about or less than about 2 g, at least about
or less than about 2.2 g, at least about or less than about 2.4 g,
at least about or less than about 2.6 g, at least about or less
than about 2.8 g, at least about or less than about 3 g, at least
about or less than about 3.2 g, at least about or less than about
3.4 g, at least about or less than about 3.6 g, at least about or
less than about 3.8 g, at least about or less than about 4 g, at
least about or less than about 4.2 g, at least about or less than
about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, at least about or less than about 6
g) of a bile acid sequestrant (e.g., cholestyramine, colesevelam,
colesevelam-HCl, ursodeoxycholic acid).
[0169] A dosage unit (e.g. an oral dosage unit) can include from,
for example, from at least about or less than about 0.1 g to at
least about or less than about 3 g (e.g. at least about or less
than about 0.1 g, at least about or less than about 0.2 g, at least
about or less than about 0.3 g, at least about or less than about
0.4 g, at least about or less than about 0.5 g, at least about or
less than about 0.6 g, at least about or less than about 0.7 g, at
least about or less than about 0.8 g, at least about or less than
about 0.9 g, at least about or less than about 1 g, at least about
or less than about 1.1 g, at least about or less than about 1.2 g,
at least about or less than about 1.3 g, at least about or less
than about 1.4 g, at least about or less than about 1.5 g, at least
about or less than about 1.6 g, at least about or less than about
1.7 g, at least about or less than about 1.8 g, at least about or
less than about 1.9 g, at least about or less than about 2 g, at
least about or less than about 2.1 g, at least about or less than
about 2.2 g, at least about or less than about 2.3 g, at least
about or less than about 2.4 g, at least about or less than about
2.5 g, at least about or less than about 2.6 g, at least about or
less than about 2.7 g, at least about or less than about 2.8 g, at
least about or less than about 2.9 g, at least about or less than
about 3 g) of a bile acid sequestrant (e.g., cholestyramine,
colesevelam, colesevelam-HCl, ursodeoxycholic acid). A dosage unit
(e.g. an oral dosage unit) can include from, for example, at least
about or less than about 1 to at least about or less than about 200
mg, at least about or less than about 5 mg to at least about or
less than about 100 mg, at least about or less than about 10 to at
least about or less than about 120 mg, at least about or less than
about 20 to at least about or less than about 100 mg, at least
about or less than about 40 mg to at least about or less than about
100 mg, at least about or less than about 5 to at least about or
less than about 80 mg, at least about or less than about 10 to at
least about or less than about 40 mg, at least about or less than
about 10 mg to at least about or less than about 60 mg, at least
about or less than about 1 mg, at least about or less than about 2
mg, at least about or less than about 3 mg, at least about or less
than about 4 mg, at least about or less than about 5 mg, at least
about or less than about 10 mg, at least about or less than about
15 mg, at least about or less than about 20 mg, at least about or
less than about 25 mg, at least about or less than about 30 mg, at
least about or less than about 35 mg, at least about or less than
about 35 mg, at least about or less than about 40 mg, at least
about or less than about 45 mg, at least about or less than about
50 mg, at least about or less than about 55 mg, at least about or
less than about 60 mg, at least about or less than about 65 mg, at
least about or less than about 70 mg, at least about or less than
about 75 mg, at least about or less than about 80 mg, at least
about or less than about 85 mg, at least about or less than about
90 mg, at least about or less than about 95 mg, at least about or
less than about 100 mg, at least about or less than about 105 mg,
at least about or less than about 110 mg, at least about or less
than about 115 mg, at least about or less than about 120 mg of a
proton pump inhibitor (e.g. omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole, tenatoprazole, leminoprazole,
dontoprazole, and ransoprazole) and from at least about or less
than about 0.1 g to at least about or less than about 3 g (e.g. at
least about or less than about 0.1 g, at least about or less than
about 0.2 g, at least about or less than about 0.3 g, at least
about or less than about 0.4 g, at least about or less than about
0.5 g, at least about or less than about 0.6 g, at least about or
less than about 0.7 g, at least about or less than about 0.8 g, at
least about or less than about 0.9 g, at least about or less than
about 1 g, at least about or less than about 1.1 g, at least about
or less than about 1.2 g, at least about or less than about 1.3 g,
at least about or less than about 1.4 g, at least about or less
than about 1.5 g, at least about or less than about 1.6 g, at least
about or less than about 1.7 g, at least about or less than about
1.8 g, at least about or less than about 1.9 g, at least about or
less than about 2 g, at least about or less than about 2.1 g, at
least about or less than about 2.2 g, at least about or less than
about 2.3 g, at least about or less than about 2.4 g, at least
about or less than about 2.5 g, at least about or less than about
2.6 g, at least about or less than about 2.7 g, at least about or
less than about 2.8 g, at least about or less than about 2.9 g, at
least about or less than about 3 g) of a bile acid sequestrant
(e.g., cholestyramine, colesevelam, colesevelam-HCl,
ursodeoxycholic acid).
[0170] A dosage unit (e.g. an oral dosage unit) can include from,
for example, from at least about or less than about 0.02 g to at
least about or less than about 0.6 g (e.g. at least about or less
than about 0.02 g, at least about or less than about 0.04 g, at
least about or less than about 0.06 g, at least about or less than
about 0.08 g, at least about or less than about 0.1 g, at least
about or less than about 0.12 g, at least about or less than about
0.14 g, at least about or less than about 0.16 g, at least about or
less than about 0.18 g, at least about or less than about 0.2 g, at
least about or less than about 0.22 g, at least about or less than
about 0.24 g, at least about or less than about 0.26 g, at least
about or less than about 0.28 g, at least about or less than about
0.3 g, at least about or less than about 0.32 g, at least about or
less than about 0.34 g, at least about or less than about 0.36 g,
at least about or less than about 0.38 g, at least about or less
than about 0.4 g, at least about or less than about 0.42 g, at
least about or less than about 0.44 g, at least about or less than
about 0.46 g, at least about or less than about 0.48 g, at least
about or less than about 0.5 g, at least about or less than about
0.52 g, at least about or less than about 0.54 g, at least about or
less than about 0.56 g, at least about or less than about 0.58 g,
at least about or less than about 0.6 g) of a bile acid sequestrant
(e.g., cholestyramine, colesevelam, colesevelam-HCl,
ursodeoxycholic acid). A dosage unit (e.g. an oral dosage unit) can
include from, for example, at least about or less than about 1 to
at least about or less than about 200 mg, at least about or less
than about 5 mg to at least about or less than about 100 mg, at
least about or less than about 10 to at least about or less than
about 120 mg, at least about or less than about 20 to at least
about or less than about 100 mg, at least about or less than about
40 mg to at least about or less than about 100 mg, at least about
or less than about 5 to at least about or less than about 80 mg, at
least about or less than about 10 to at least about or less than
about 40 mg, at least about or less than about 10 mg to at least
about or less than about 60 mg, at least about or less than about 1
mg, at least about or less than about 2 mg, at least about or less
than about 3 mg, at least about or less than about 4 mg, at least
about or less than about 5 mg, at least about or less than about 10
mg, at least about or less than about 15 mg, at least about or less
than about 20 mg, at least about or less than about 25 mg, at least
about or less than about 30 mg, at least about or less than about
35 mg, at least about or less than about 35 mg, at least about or
less than about 40 mg, at least about or less than about 45 mg, at
least about or less than about 50 mg, at least about or less than
about 55 mg, at least about or less than about 60 mg, at least
about or less than about 65 mg, at least about or less than about
70 mg, at least about or less than about 75 mg, at least about or
less than about 80 mg, at least about or less than about 85 mg, at
least about or less than about 90 mg, at least about or less than
about 95 mg, at least about or less than about 100 mg, at least
about or less than about 105 mg, at least about or less than about
110 mg, at least about or less than about 115 mg, at least about or
less than about 120 mg of a proton pump inhibitor (e.g. omeprazole,
esomeprazole, lansoprazole, pantoprazole, rabeprazole,
tenatoprazole, leminoprazole, dontoprazole, and ransoprazole) and
from at least about or less than about 0.02 g to at least about or
less than about 0.6 g (e.g. at least about or less than about 0.02
g, at least about or less than about 0.04 g, at least about or less
than about 0.06 g, at least about or less than about 0.08 g, at
least about or less than about 0.1 g, at least about or less than
about 0.12 g, at least about or less than about 0.14 g, at least
about or less than about 0.16 g, at least about or less than about
0.18 g, at least about or less than about 0.2 g, at least about or
less than about 0.22 g, at least about or less than about 0.24 g,
at least about or less than about 0.26 g, at least about or less
than about 0.28 g, at least about or less than about 0.3 g, at
least about or less than about 0.32 g, at least about or less than
about 0.34 g, at least about or less than about 0.36 g, at least
about or less than about 0.38 g, at least about or less than about
0.4 g, at least about or less than about 0.42 g, at least about or
less than about 0.44 g, at least about or less than about 0.46 g,
at least about or less than about 0.48 g, at least about or less
than about 0.5 g, at least about or less than about 0.52 g, at
least about or less than about 0.54 g, at least about or less than
about 0.56 g, at least about or less than about 0.58 g, at least
about or less than about 0.6 g) of a bile acid sequestrant (e.g.,
cholestyramine, colesevelam, colesevelam-HCl, ursodeoxycholic
acid).
[0171] A dosage unit (e.g. an oral dosage unit) can include from,
for example, from at least about or less than about 0.01 g to at
least about or less than about 0.3 g (e.g. at least about or less
than about 0.01 g, at least about or less than about 0.02 g, at
least about or less than about 0.03 g, at least about or less than
about 0.04 g, at least about or less than about 0.05 g, at least
about or less than about 0.06 g, at least about or less than about
0.07 g, at least about or less than about 0.08 g, at least about or
less than about 0.09 g, at least about or less than about 0.1 g, at
least about or less than about 0.11 g, at least about or less than
about 0.12 g, at least about or less than about 0.13 g, at least
about or less than about 0.14 g, at least about or less than about
0.15 g, at least about or less than about 0.16 g, at least about or
less than about 0.17 g, at least about or less than about 0.18 g,
at least about or less than about 0.19 g, at least about or less
than about 0.2 g, at least about or less than about 0.21 g, at
least about or less than about 0.22 g, at least about or less than
about 0.23 g, at least about or less than about 0.24 g, at least
about or less than about 0.25 g, at least about or less than about
0.26 g, at least about or less than about 0.27 g, at least about or
less than about 0.28 g, at least about or less than about 0.29 g,
at least about or less than about 0.3 g) of a bile acid sequestrant
(e.g., cholestyramine, colesevelam, colesevelam-HCl,
ursodeoxycholic acid, sevelamer). A dosage unit (e.g. an oral
dosage unit) can include from, for example, at least about or less
than about 1 to at least about or less than about 200 mg, at least
about or less than about 5 mg to at least about or less than about
100 mg, at least about or less than about 10 to at least about or
less than about 120 mg, at least about or less than about 20 to at
least about or less than about 100 mg, at least about or less than
about 40 mg to at least about or less than about 100 mg, at least
about or less than about 5 to at least about or less than about 80
mg, at least about or less than about 10 to at least about or less
than about 40 mg, at least about or less than about 10 mg to at
least about or less than about 60 mg, at least about or less than
about 1 mg, at least about or less than about 2 mg, at least about
or less than about 3 mg, at least about or less than about 4 mg, at
least about or less than about 5 mg, at least about or less than
about 10 mg, at least about or less than about 15 mg, at least
about or less than about 20 mg, at least about or less than about
25 mg, at least about or less than about 30 mg, at least about or
less than about 35 mg, at least about or less than about 35 mg, at
least about or less than about 40 mg, at least about or less than
about 45 mg, at least about or less than about 50 mg, at least
about or less than about 55 mg, at least about or less than about
60 mg, at least about or less than about 65 mg, at least about or
less than about 70 mg, at least about or less than about 75 mg, at
least about or less than about 80 mg, at least about or less than
about 85 mg, at least about or less than about 90 mg, at least
about or less than about 95 mg, at least about or less than about
100 mg, at least about or less than about 105 mg, at least about or
less than about 110 mg, at least about or less than about 115 mg,
at least about or less than about 120 mg of a proton pump inhibitor
(e.g. omeprazole, esomeprazole, lansoprazole, pantoprazole,
rabeprazole, tenatoprazole, leminoprazole, dontoprazole, and
ransoprazole) and from at least about or less than about 0.01 g to
at least about or less than about 0.3 g (e.g. at least about or
less than about 0.01 g, at least about or less than about 0.02 g,
at least about or less than about 0.03 g, at least about or less
than about 0.04 g, at least about or less than about 0.05 g, at
least about or less than about 0.06 g, at least about or less than
about 0.07 g, at least about or less than about 0.08 g, at least
about or less than about 0.09 g, at least about or less than about
0.1 g, at least about or less than about 0.11 g, at least about or
less than about 0.12 g, at least about or less than about 0.13 g,
at least about or less than about 0.14 g, at least about or less
than about 0.15 g, at least about or less than about 0.16 g, at
least about or less than about 0.17 g, at least about or less than
about 0.18 g, at least about or less than about 0.19 g, at least
about or less than about 0.2 g, at least about or less than about
0.21 g, at least about or less than about 0.22 g, at least about or
less than about 0.23 g, at least about or less than about 0.24 g,
at least about or less than about 0.25 g, at least about or less
than about 0.26 g, at least about or less than about 0.27 g, at
least about or less than about 0.28 g, at least about or less than
about 0.29 g, at least about or less than about 0.3 g) of a bile
acid sequestrant (e.g., cholestyramine, colesevelam,
colesevelam-HCl, ursodeoxycholic acid, sevelamer).
[0172] A dosage unit (e.g. an oral dosage unit) can include from,
for example, from at least about or less than about 5 g to at least
about or less than about 150 g (e.g. at least about or less than
about 5 g, at least about or less than about 10 g, at least about
or less than about 15 g, at least about or less than about 20 g, at
least about or less than about 25 g, at least about or less than
about 30 g, at least about or less than about 35 g, at least about
or less than about 40 g, at least about or less than about 45 g, at
least about or less than about 50 g, at least about or less than
about 55 g, at least about or less than about 60 g, at least about
or less than about 65 g, at least about or less than about 70 g, at
least about or less than about 75 g, at least about or less than
about 80 g, at least about or less than about 85 g, at least about
or less than about 90 g, at least about or less than about 95 g, at
least about or less than about 100 g, at least about or less than
about 105 g, at least about or less than about 110 g, at least
about or less than about 115 g, at least about or less than about
120 g, at least about or less than about 125 g, at least about or
less than about 130 g, at least about or less than about 135 g, at
least about or less than about 140 g, at least about or less than
about 145 g, at least about or less than about 150 g) of a bile
acid sequestrant (e.g., cholestyramine, colesevelam,
colesevelam-HCl, ursodeoxycholic acid). A dosage unit (e.g. an oral
dosage unit) can include from, for example, at least about or less
than about 1 to 200 mg, at least about or less than about 5 mg to
at least about or less than about 100 mg, at least about or less
than about 10 to at least about or less than about 120 mg, at least
about or less than about 20 to at least about or less than about
100 mg, at least about or less than about 40 mg to at least about
or less than about 100 mg, at least about or less than about 5 to
at least about or less than about 80 mg, at least about or less
than about 10 to at least about or less than about 40 mg, at least
about or less than about 10 mg to at least about or less than about
60 mg, at least about or less than about 1 mg, at least about or
less than about 2 mg, at least about or less than about 3 mg, at
least about or less than about 4 mg, at least about or less than
about 5 mg, at least about or less than about 10 mg, at least about
or less than about 15 mg, at least about or less than about 20 mg,
at least about or less than about 25 mg, at least about or less
than about 30 mg, at least about or less than about 35 mg, at least
about or less than about 35 mg, at least about or less than about
40 mg, at least about or less than about 45 mg, at least about or
less than about 50 mg, at least about or less than about 55 mg, at
least about or less than about 60 mg, at least about or less than
about 65 mg, at least about or less than about 70 mg, at least
about or less than about 75 mg, at least about or less than about
80 mg, at least about or less than about 85 mg, at least about or
less than about 90 mg, at least about or less than about 95 mg, at
least about or less than about 100 mg, at least about or less than
about 105 mg, at least about or less than about 110 mg, at least
about or less than about 115 mg, at least about or less than about
120 mg of a proton pump inhibitor (e.g. omeprazole, esomeprazole,
lansoprazole, pantoprazole, rabeprazole, tenatoprazole,
leminoprazole, dontoprazole, and ransoprazole) and from at least
about or less than about 5 g to at least about or less than about
150 g (e.g. at least about or less than about 5 g, at least about
or less than about 10 g, at least about or less than about 15 g, at
least about or less than about 20 g, at least about or less than
about 25 g, at least about or less than about 30 g, at least about
or less than about 35 g, at least about or less than about 40 g, at
least about or less than about 45 g, at least about or less than
about 50 g, at least about or less than about 55 g, at least about
or less than about 60 g, at least about or less than about 65 g, at
least about or less than about 70 g, at least about or less than
about 75 g, at least about or less than about 80 g, at least about
or less than about 85 g, at least about or less than about 90 g, at
least about or less than about 95 g, at least about or less than
about 100 g, at least about or less than about 105 g, at least
about or less than about 110 g, at least about or less than about
115 g, at least about or less than about 120 g, at least about or
less than about 125 g, at least about or less than about 130 g, at
least about or less than about 135 g, at least about or less than
about 140 g, at least about or less than about 145 g, at least
about or less than about 150 g) of a bile acid sequestrant (e.g.,
cholestyramine, colesevelam, colesevelam-HCl, ursodeoxycholic
acid).
[0173] A dosage unit (e.g. an oral dosage unit) can include from,
for example, from at least about or less than about 2 g to at least
about or less than about 60 g (e.g. at least about or less than
about 2 g, at least about or less than about 4 g, at least about or
less than about 6 g, at least about or less than about 8 g, at
least about or less than about 10 g, at least about or less than
about 12 g, at least about or less than about 14 g, at least about
or less than about 16 g, at least about or less than about 18 g, at
least about or less than about 20 g, at least about or less than
about 22 g, at least about or less than about 24 g, at least about
or less than about 26 g, at least about or less than about 28 g, at
least about or less than about 30 g, at least about or less than
about 32 g, at least about or less than about 34 g, at least about
or less than about 36 g, at least about or less than about 38 g, at
least about or less than about 40 g, at least about or less than
about 42 g, at least about or less than about 44 g, at least about
or less than about 46 g, at least about or less than about 48 g, at
least about or less than about 50 g, at least about or less than
about 52 g, at least about or less than about 54 g, at least about
or less than about 56 g, at least about or less than about 58 g, at
least about or less than about 60 g) of a bile acid sequestrant
(e.g., cholestyramine, colesevelam, colesevelam-HCl,
ursodeoxycholic acid). A dosage unit (e.g. an oral dosage unit) can
include from, for example, at least about or less than about 1 to
at least about or less than about 200 mg, at least about or less
than about 5 mg to at least about or less than about 100 mg, at
least about or less than about 10 to at least about or less than
about 120 mg, at least about or less than about 20 to at least
about or less than about 100 mg, at least about or less than about
40 mg to at least about or less than about 100 mg, at least about
or less than about 5 to at least about or less than about 80 mg, at
least about or less than about 10 to at least about or less than
about 40 mg, at least about or less than about 10 mg to at least
about or less than about 60 mg, at least about or less than about 1
mg, at least about or less than about 2 mg, at least about or less
than about 3 mg, at least about or less than about 4 mg, at least
about or less than about 5 mg, at least about or less than about 10
mg, at least about or less than about 15 mg, at least about or less
than about 20 mg, at least about or less than about 25 mg, at least
about or less than about 30 mg, at least about or less than about
35 mg, at least about or less than about 35 mg, at least about or
less than about 40 mg, at least about or less than about 45 mg, at
least about or less than about 50 mg, at least about or less than
about 55 mg, at least about or less than about 60 mg, at least
about or less than about 65 mg, at least about or less than about
70 mg, at least about or less than about 75 mg, at least about or
less than about 80 mg, at least about or less than about 85 mg, at
least about or less than about 90 mg, at least about or less than
about 95 mg, at least about or less than about 100 mg, at least
about or less than about 105 mg, at least about or less than about
110 mg, at least about or less than about 115 mg, at least about or
less than about 120 mg of a proton pump inhibitor (e.g. omeprazole,
esomeprazole, lansoprazole, pantoprazole, rabeprazole,
tenatoprazole, leminoprazole, dontoprazole, and ransoprazole) and
from at least about or less than about 2 g to at least about or
less than about 60 g (e.g. at least about or less than about 2 g,
at least about or less than about 4 g, at least about or less than
about 6 g, at least about or less than about 8 g, at least about or
less than about 10 g, at least about or less than about 12 g, at
least about or less than about 14 g, at least about or less than
about 16 g, at least about or less than about 18 g, at least about
or less than about 20 g, at least about or less than about 22 g, at
least about or less than about 24 g, at least about or less than
about 26 g, at least about or less than about 28 g, at least about
or less than about 30 g, at least about or less than about 32 g, at
least about or less than about 34 g, at least about or less than
about 36 g, at least about or less than about 38 g, at least about
or less than about 40 g, at least about or less than about 42 g, at
least about or less than about 44 g, at least about or less than
about 46 g, at least about or less than about 48 g, at least about
or less than about 50 g, at least about or less than about 52 g, at
least about or less than about 54 g, at least about or less than
about 56 g, at least about or less than about 58 g, at least about
or less than about 60 g) of a bile acid sequestrant (e.g.,
cholestyramine, colesevelam, colesevelam-HCl, ursodeoxycholic
acid).
[0174] A dosage unit (e.g. an oral dosage unit) can include from,
for example, from at least about or less than about 10 g to at
least about or less than about 300 g (e.g. at least about or less
than about 10 g, at least about or less than about 20 g, at least
about or less than about 30 g, at least about or less than about 40
g, at least about or less than about 50 g, at least about or less
than about 60 g, at least about or less than about 70 g, at least
about or less than about 80 g, at least about or less than about 90
g, at least about or less than about 100 g, at least about or less
than about 110 g, at least about or less than about 120 g, at least
about or less than about 130 g, at least about or less than about
140 g, at least about or less than about 150 g, at least about or
less than about 160 g, at least about or less than about 170 g, at
least about or less than about 180 g, at least about or less than
about 190 g, at least about or less than about 200 g, at least
about or less than about 210 g, at least about or less than about
220 g, at least about or less than about 230 g, at least about or
less than about 240 g, at least about or less than about 250 g, at
least about or less than about 260 g, at least about or less than
about 270 g, at least about or less than about 280 g, at least
about or less than about 290 g, at least about or less than about
300 g) of a bile acid sequestrant (e.g., cholestyramine,
colesevelam, colesevelam-HCl, ursodeoxycholic acid). A dosage unit
(e.g. an oral dosage unit) can include from, for example, at least
about or less than about 1 to at least about or less than about 200
mg, at least about or less than about 5 mg to at least about or
less than about 100 mg, at least about or less than about 10 to at
least about or less than about 120 mg, at least about or less than
about 20 to at least about or less than about 100 mg, at least
about or less than about 40 mg to at least about or less than about
100 mg, at least about or less than about 5 to at least about or
less than about 80 mg, at least about or less than about 10 to at
least about or less than about 40 mg, at least about or less than
about 10 mg to at least about or less than about 60 mg, at least
about or less than about 1 mg, at least about or less than about 2
mg, at least about or less than about 3 mg, at least about or less
than about 4 mg, at least about or less than about 5 mg, at least
about or less than about 10 mg, at least about or less than about
15 mg, at least about or less than about 20 mg, at least about or
less than about 25 mg, at least about or less than about 30 mg, at
least about or less than about 35 mg, at least about or less than
about 35 mg, at least about or less than about 40 mg, at least
about or less than about 45 mg, at least about or less than about
50 mg, at least about or less than about 55 mg, at least about or
less than about 60 mg, at least about or less than about 65 mg, at
least about or less than about 70 mg, at least about or less than
about 75 mg, at least about or less than about 80 mg, at least
about or less than about 85 mg, at least about or less than about
90 mg, at least about or less than about 95 mg, at least about or
less than about 100 mg, at least about or less than about 105 mg,
at least about or less than about 110 mg, at least about or less
than about 115 mg, at least about or less than about 120 mg of a
proton pump inhibitor (e.g. omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole, tenatoprazole, leminoprazole,
dontoprazole, and ransoprazole) and from at least about or less
than about 10 g to at least about or less than about 300 g (e.g. at
least about or less than about 10 g, at least about or less than
about 20 g, at least about or less than about 30 g, at least about
or less than about 40 g, at least about or less than about 50 g, at
least about or less than about 60 g, at least about or less than
about 70 g, at least about or less than about 80 g, at least about
or less than about 90 g, at least about or less than about 100 g,
at least about or less than about 110 g, at least about or less
than about 120 g, at least about or less than about 130 g, at least
about or less than about 140 g, at least about or less than about
150 g, at least about or less than about 160 g, at least about or
less than about 170 g, at least about or less than about 180 g, at
least about or less than about 190 g, at least about or less than
about 200 g, at least about or less than about 210 g, at least
about or less than about 220 g, at least about or less than about
230 g, at least about or less than about 240 g, at least about or
less than about 250 g, at least about or less than about 260 g, at
least about or less than about 270 g, at least about or less than
about 280 g, at least about or less than about 290 g, at least
about or less than about 300 g) of a bile acid sequestrant (e.g.,
cholestyramine, colesevelam, colesevelam-HCl, ursodeoxycholic
acid).
In certain embodiments, the dosage unit comprises at least about or
less than about 5 mg of at least one proton pump inhibitor and at
least about or less than about 1 g, at least about or less than
about 2 g, at least about or less than about 3 g, at least about or
less than about 4 g, at least about or less than about 5 g, at
least about or less than about 6 g, at least about or less than
about 7 g, at least about or less than about 8 g, at least about or
less than about 9 g, at least about or less than about 10 g, at
least about or less than about 11 g, at least about or less than
about 12 g, at least about or less than about 13 g, at least about
or less than about 14 g, at least about or less than about 15 g, at
least about or less than about 16 g, at least about or less than
about 17 g, at least about or less than about 18 g, at least about
or less than about 19 g, at least about or less than about 20 g, at
least about or less than about 21 g, at least about or less than
about 22 g, at least about or less than about 23 g, at least about
or less than about 24 g, at least about or less than about 25 g, at
least about or less than about 26 g, at least about or less than
about 27 g, at least about or less than about 28 g, at least about
or less than about 29 g, or at least about or less than about 30 g
of at least one bile acid sequestrant. In certain embodiments, the
dosage unit comprises at least about or less than about 10 mg of at
least one proton pump inhibitor and at least about or less than
about 1 g, at least about or less than about 2 g, at least about or
less than about 3 g, at least about or less than about 4 g, at
least about or less than about 5 g, at least about or less than
about 6 g, at least about or less than about 7 g, at least about or
less than about 8 g, at least about or less than about 9 g, at
least about or less than about 10 g, at least about or less than
about 11 g, at least about or less than about 12 g, at least about
or less than about 13 g, at least about or less than about 14 g, at
least about or less than about 15 g, at least about or less than
about 16 g, at least about or less than about 17 g, at least about
or less than about 18 g, at least about or less than about 19 g, at
least about or less than about 20 g, at least about or less than
about 21 g, at least about or less than about 22 g, at least about
or less than about 23 g, at least about or less than about 24 g, at
least about or less than about 25 g, at least about or less than
about 26 g, at least about or less than about 27 g, at least about
or less than about 28 g, at least about or less than about 29 g, or
at least about or less than about 30 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 15 mg of at least one proton pump
inhibitor and at least about or less than about 1 g, at least about
or less than about 2 g, at least about or less than about 3 g, at
least about or less than about 4 g, at least about or less than
about 5 g, at least about or less than about 6 g, at least about or
less than about 7 g, at least about or less than about 8 g, at
least about or less than about 9 g, at least about or less than
about 10 g, at least about or less than about 11 g, at least about
or less than about 12 g, at least about or less than about 13 g, at
least about or less than about 14 g, at least about or less than
about 15 g, at least about or less than about 16 g, at least about
or less than about 17 g, at least about or less than about 18 g, at
least about or less than about 19 g, at least about or less than
about 20 g, at least about or less than about 21 g, at least about
or less than about 22 g, at least about or less than about 23 g, at
least about or less than about 24 g, at least about or less than
about 25 g, at least about or less than about 26 g, at least about
or less than about 27 g, at least about or less than about 28 g, at
least about or less than about 29 g, or at least about or less than
about 30 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 20 mg of at least one proton pump inhibitor and at least
about or less than about 1 g, at least about or less than about 2
g, at least about or less than about 3 g, at least about or less
than about 4 g, at least about or less than about 5 g, at least
about or less than about 6 g, at least about or less than about 7
g, at least about or less than about 8 g, at least about or less
than about 9 g, at least about or less than about 10 g, at least
about or less than about 11 g, at least about or less than about 12
g, at least about or less than about 13 g, at least about or less
than about 14 g, at least about or less than about 15 g, at least
about or less than about 16 g, at least about or less than about 17
g, at least about or less than about 18 g, at least about or less
than about 19 g, at least about or less than about 20 g, at least
about or less than about 21 g, at least about or less than about 22
g, at least about or less than about 23 g, at least about or less
than about 24 g, at least about or less than about 25 g, at least
about or less than about 26 g, at least about or less than about 27
g, at least about or less than about 28 g, at least about or less
than about 29 g, or at least about or less than about 30 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 25 mg of at least
one proton pump inhibitor and at least about or less than about 1
g, at least about or less than about 2 g, at least about or less
than about 3 g, at least about or less than about 4 g, at least
about or less than about 5 g, at least about or less than about 6
g, at least about or less than about 7 g, at least about or less
than about 8 g, at least about or less than about 9 g, at least
about or less than about 10 g, at least about or less than about 11
g, at least about or less than about 12 g, at least about or less
than about 13 g, at least about or less than about 14 g, at least
about or less than about 15 g, at least about or less than about 16
g, at least about or less than about 17 g, at least about or less
than about 18 g, at least about or less than about 19 g, at least
about or less than about 20 g, at least about or less than about 21
g, at least about or less than about 22 g, at least about or less
than about 23 g, at least about or less than about 24 g, at least
about or less than about 25 g, at least about or less than about 26
g, at least about or less than about 27 g, at least about or less
than about 28 g, at least about or less than about 29 g, or at
least about or less than about 30 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 30 mg of at least one proton pump
inhibitor and at least about or less than about 1 g, at least about
or less than about 2 g, at least about or less than about 3 g, at
least about or less than about 4 g, at least about or less than
about 5 g, at least about or less than about 6 g, at least about or
less than about 7 g, at least about or less than about 8 g, at
least about or less than about 9 g, at least about or less than
about 10 g, at least about or less than about 11 g, at least about
or less than about 12 g, at least about or less than about 13 g, at
least about or less than about 14 g, at least about or less than
about 15 g, at least about or less than about 16 g, at least about
or less than about 17 g, at least about or less than about 18 g, at
least about or less than about 19 g, at least about or less than
about 20 g, at least about or less than about 21 g, at least about
or less than about 22 g, at least about or less than about 23 g, at
least about or less than about 24 g, at least about or less than
about 25 g, at least about or less than about 26 g, at least about
or less than about 27 g, at least about or less than about 28 g, at
least about or less than about 29 g, or at least about or less than
about 30 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 35 mg of at least one proton pump inhibitor and at least
about or less than about 1 g, at least about or less than about 2
g, at least about or less than about 3 g, at least about or less
than about 4 g, at least about or less than about 5 g, at least
about or less than about 6 g, at least about or less than about 7
g, at least about or less than about 8 g, at least about or less
than about 9 g, at least about or less than about 10 g, at least
about or less than about 11 g, at least about or less than about 12
g, at least about or less than about 13 g, at least about or less
than about 14 g, at least about or less than about 15 g, at least
about or less than about 16 g, at least about or less than about 17
g, at least about or less than about 18 g, at least about or less
than about 19 g, at least about or less than about 20 g, at least
about or less than about 21 g, at least about or less than about 22
g, at least about or less than about 23 g, at least about or less
than about 24 g, at least about or less than about 25 g, at least
about or less than about 26 g, at least about or less than about 27
g, at least about or less than about 28 g, at least about or less
than about 29 g, or at least about or less than about 30 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 40 mg of at least
one proton pump inhibitor and at least about or less than about 1
g, at least about or less than about 2 g, at least about or less
than about 3 g, at least about or less than about 4 g, at least
about or less than about 5 g, at least about or less than about 6
g, at least about or less than about 7 g, at least about or less
than about 8 g, at least about or less than about 9 g, at least
about or less than about 10 g, at least about or less than about 11
g, at least about or less than about 12 g, at least about or less
than about 13 g, at least about or less than about 14 g, at least
about or less than about 15 g, at least about or less than about 16
g, at least about or less than about 17 g, at least about or less
than about 18 g, at least about or less than about 19 g, at least
about or less than about 20 g, at least about or less than about 21
g, at least about or less than about 22 g, at least about or less
than about 23 g, at least about or less than about 24 g, at least
about or less than about 25 g, at least about or less than about 26
g, at least about or less than about 27 g, at least about or less
than about 28 g, at least about or less than about 29 g, or at
least about or less than about 30 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 45 mg of at least one proton pump
inhibitor and at least about or less than about 1 g, at least about
or less than about 2 g, at least about or less than about 3 g, at
least about or less than about 4 g, at least about or less than
about 5 g, at least about or less than about 6 g, at least about or
less than about 7 g, at least about or less than about 8 g, at
least about or less than about 9 g, at least about or less than
about 10 g, at least about or less than about 11 g, at least about
or less than about 12 g, at least about or less than about 13 g, at
least about or less than about 14 g, at least about or less than
about 15 g, at least about or less than about 16 g, at least about
or less than about 17 g, at least about or less than about 18 g, at
least about or less than about 19 g, at least about or less than
about 20 g, at least about or less than about 21 g, at least about
or less than about 22 g, at least about or less than about 23 g, at
least about or less than about 24 g, at least about or less than
about 25 g, at least about or less than about 26 g, at least about
or less than about 27 g, at least about or less than about 28 g, at
least about or less than about 29 g, or at least about or less than
about 30 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 50 mg of at least one proton pump inhibitor and at least
about or less than about 1 g, at least about or less than about 2
g, at least about or less than about 3 g, at least about or less
than about 4 g, at least about or less than about 5 g, at least
about or less than about 6 g, at least about or less than about 7
g, at least about or less than about 8 g, at least about or less
than about 9 g, at least about or less than about 10 g, at least
about or less than about 11 g, at least about or less than about 12
g, at least about or less than about 13 g, at least about or less
than about 14 g, at least about or less than about 15 g, at least
about or less than about 16 g, at least about or less than about 17
g, at least about or less than about 18 g, at least about or less
than about 19 g, at least about or less than about 20 g, at least
about or less than about 21 g, at least about or less than about 22
g, at least about or less than about 23 g, at least about or less
than about 24 g, at least about or less than about 25 g, at least
about or less than about 26 g, at least about or less than about 27
g, at least about or less than about 28 g, at least about or less
than about 29 g, or at least about or less than about 30 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 55 mg of at least
one proton pump inhibitor and at least about or less than about 1
g, at least about or less than about 2 g, at least about or less
than about 3 g, at least about or less than about 4 g, at least
about or less than about 5 g, at least about or less than about 6
g, at least about or less than about 7 g, at least about or less
than about 8 g, at least about or less than about 9 g, at least
about or less than about 10 g, at least about or less than about 11
g, at least about or less than about 12 g, at least about or less
than about 13 g, at least about or less than about 14 g, at least
about or less than about 15 g, at least about or less than about 16
g, at least about or less than about 17 g, at least about or less
than about 18 g, at least about or less than about 19 g, at least
about or less than about 20 g, at least about or less than about 21
g, at least about or less than about 22 g, at least about or less
than about 23 g, at least about or less than about 24 g, at least
about or less than about 25 g, at least about or less than about 26
g, at least about or less than about 27 g, at least about or less
than about 28 g, at least about or less than about 29 g, or at
least about or less than about 30 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 60 mg of at least one proton pump
inhibitor and at least about or less than about 1 g, at least about
or less than about 2 g, at least about or less than about 3 g, at
least about or less than about 4 g, at least about or less than
about 5 g, at least about or less than about 6 g, at least about or
less than about 7 g, at least about or less than about 8 g, at
least about or less than about 9 g, at least about or less than
about 10 g, at least about or less than about 11 g, at least about
or less than about 12 g, at least about or less than about 13 g, at
least about or less than about 14 g, at least about or less than
about 15 g, at least about or less than about 16 g, at least about
or less than about 17 g, at least about or less than about 18 g, at
least about or less than about 19 g, at least about or less than
about 20 g, at least about or less than about 21 g, at least about
or less than about 22 g, at least about or less than about 23 g, at
least about or less than about 24 g, at least about or less than
about 25 g, at least about or less than about 26 g, at least about
or less than about 27 g, at least about or less than about 28 g, at
least about or less than about 29 g, or at least about or less than
about 30 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 65 mg of at least one proton pump inhibitor and at least
about or less than about 1 g, at least about or less than about 2
g, at least about or less than about 3 g, at least about or less
than about 4 g, at least about or less than about 5 g, at least
about or less than about 6 g, at least about or less than about 7
g, at least about or less than about 8 g, at least about or less
than about 9 g, at least about or less than about 10 g, at least
about or less than about 11 g, at least about or less than about 12
g, at least about or less than about 13 g, at least about or less
than about 14 g, at least about or less than about 15 g, at least
about or less than about 16 g, at least about or less than about 17
g, at least about or less than about 18 g, at least about or less
than about 19 g, at least about or less than about 20 g, at least
about or less than about 21 g, at least about or less than about 22
g, at least about or less than about 23 g, at least about or less
than about 24 g, at least about or less than about 25 g, at least
about or less than about 26 g, at least about or less than about 27
g, at least about or less than about 28 g, at least about or less
than about 29 g, or at least about or less than about 30 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 70 mg of at least
one proton pump inhibitor and at least about or less than about 1
g, at least about or less than about 2 g, at least about or less
than about 3 g, at least about or less than about 4 g, at least
about or less than about 5 g, at least about or less than about 6
g, at least about or less than about 7 g, at least about or less
than about 8 g, at least about or less than about 9 g, at least
about or less than about 10 g, at least about or less than about 11
g, at least about or less than about 12 g, at least about or less
than about 13 g, at least about or less than about 14 g, at least
about or less than about 15 g, at least about or less than about 16
g, at least about or less than about 17 g, at least about or less
than about 18 g, at least about or less than about 19 g, at least
about or less than about 20 g, at least about or less than about 21
g, at least about or less than about 22 g, at least about or less
than about 23 g, at least about or less than about 24 g, at least
about or less than about 25 g, at least about or less than about 26
g, at least about or less than about 27 g, at least about or less
than about 28 g, at least about or less than about 29 g, or at
least about or less than about 30 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 75 mg of at least one proton pump
inhibitor and at least about or less than about 1 g, at least about
or less than about 2 g, at least about or less than about 3 g, at
least about or less than about 4 g, at least about or less than
about 5 g, at least about or less than about 6 g, at least about or
less than about 7 g, at least about or less than about 8 g, at
least about or less than about 9 g, at least about or less than
about 10 g, at least about or less than about 11 g, at least about
or less than about 12 g, at least about or less than about 13 g, at
least about or less than about 14 g, at least about or less than
about 15 g, at least about or less than about 16 g, at least about
or less than about 17 g, at least about or less than about 18 g, at
least about or less than about 19 g, at least about or less than
about 20 g, at least about or less than about 21 g, at least about
or less than about 22 g, at least about or less than about 23 g, at
least about or less than about 24 g, at least about or less than
about 25 g, at least about or less than about 26 g, at least about
or less than about 27 g, at least about or less than about 28 g, at
least about or less than about 29 g, or at least about or less than
about 30 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 80 mg of at least one proton pump inhibitor and at least
about or less than about 1 g, at least about or less than about 2
g, at least about or less than about 3 g, at least about or less
than about 4 g, at least about or less than about 5 g, at least
about or less than about 6 g, at least about or less than about 7
g, at least about or less than about 8 g, at least about or less
than about 9 g, at least about or less than about 10 g, at least
about or less than about 11 g, at least about or less than about 12
g, at least about or less than about 13 g, at least about or less
than about 14 g, at least about or less than about 15 g, at least
about or less than about 16 g, at least about or less than about 17
g, at least about or less than about 18 g, at least about or less
than about 19 g, at least about or less than about 20 g, at least
about or less than about 21 g, at least about or less than about 22
g, at least about or less than about 23 g, at least about or less
than about 24 g, at least about or less than about 25 g, at least
about or less than about 26 g, at least about or less than about 27
g, at least about or less than about 28 g, at least about or less
than about 29 g, or at least about or less than about 30 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 85 mg of at least
one proton pump inhibitor and at least about or less than about 1
g, at least about or less than about 2 g, at least about or less
than about 3 g, at least about or less than about 4 g, at least
about or less than about 5 g, at least about or less than about 6
g, at least about or less than about 7 g, at least about or less
than about 8 g, at least about or less than about 9 g, at least
about or less than about 10 g, at least about or less than about 11
g, at least about or less than about 12 g, at least about or less
than about 13 g, at least about or less than about 14 g, at least
about or less than about 15 g, at least about or less than about 16
g, at least about or less than about 17 g, at least about or less
than about 18 g, at least about or less than about 19 g, at least
about or less than about 20 g, at least about or less than about 21
g, at least about or less than about 22 g, at least about or less
than about 23 g, at least about or less than about 24 g, at least
about or less than about 25 g, at least about or less than about 26
g, at least about or less than about 27 g, at least about or less
than about 28 g, at least about or less than about 29 g, or at
least about or less than about 30 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 90 mg of at least one proton pump
inhibitor and at least about or less than about 1 g, at least about
or less than about 2 g, at least about or less than about 3 g, at
least about or less than about 4 g, at least about or less than
about 5 g, at least about or less than about 6 g, at least about or
less than about 7 g, at least about or less than about 8 g, at
least about or less than about 9 g, at least about or less than
about 10 g, at least about or less than about 11 g, at least about
or less than about 12 g, at least about or less than about 13 g, at
least about or less than about 14 g, at least about or less than
about 15 g, at least about or less than about 16 g, at least about
or less than about 17 g, at least about or less than about 18 g, at
least about or less than about 19 g, at least about or less than
about 20 g, at least about or less than about 21 g, at least about
or less than about 22 g, at least about or less than about 23 g, at
least about or less than about 24 g, at least about or less than
about 25 g, at least about or less than about 26 g, at least about
or less than about 27 g, at least about or less than about 28 g, at
least about or less than about 29 g, or at least about or less than
about 30 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 95 mg of at least one proton pump inhibitor and at least
about or less than about 1 g, at least about or less than about 2
g, at least about or less than about 3 g, at least about or less
than about 4 g, at least about or less than about 5 g, at least
about or less than about 6 g, at least about or less than about 7
g, at least about or less than about 8 g, at least about or less
than about 9 g, at least about or less than about 10 g, at least
about or less than about 11 g, at least about or less than about 12
g, at least about or less than about 13 g, at least about or less
than about 14 g, at least about or less than about 15 g, at least
about or less than about 16 g, at least about or less than about 17
g, at least about or less than about 18 g, at least about or less
than about 19 g, at least about or less than about 20 g, at least
about or less than about 21 g, at least about or less than about 22
g, at least about or less than about 23 g, at least about or less
than about 24 g, at least about or less than about 25 g, at least
about or less than about 26 g, at least about or less than about 27
g, at least about or less than about 28 g, at least about or less
than about 29 g, or at least about or less than about 30 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 100 mg of at least
one proton pump inhibitor and at least about or less than about 1
g, at least about or less than about 2 g, at least about or less
than about 3 g, at least about or less than about 4 g, at least
about or less than about 5 g, at least about or less than about 6
g, at least about or less than about 7 g, at least about or less
than about 8 g, at least about or less than about 9 g, at least
about or less than about 10 g, at least about or less than about 11
g, at least about or less than about 12 g, at least about or less
than about 13 g, at least about or less than about 14 g, at least
about or less than about 15 g, at least about or less than about 16
g, at least about or less than about 17 g, at least about or less
than about 18 g, at least about or less than about 19 g, at least
about or less than about 20 g, at least about or less than about 21
g, at least about or less than about 22 g, at least about or less
than about 23 g, at least about or less than about 24 g, at least
about or less than about 25 g, at least about or less than about 26
g, at least about or less than about 27 g, at least about or less
than about 28 g, at least about or less than about 29 g, or at
least about or less than about 30 g of at least one bile acid
sequestrant. In certain embodiments the at least one proton pump
inhibitor is omeprazole. In certain embodiments the at least one
proton pump inhibitor is esomeprazole. In certain embodiments the
at least one proton pump inhibitor is lansoprazole. In certain
embodiments the at least one proton pump inhibitor is pantoprazole.
In certain embodiments the at least one proton pump inhibitor is
rabeprazole. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole. In certain embodiments the at least one
bile acid sequestrant is cholestyramine. In certain embodiments the
at least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one bile acid sequestrant is
colesevelam-HCl. In certain embodiments the at least one bile acid
sequestrant is colestipol. In certain embodiments the at least one
proton pump inhibitor is omeprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is omeprazole and the at least one bile
acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is omeprazole and the at least one
bile acid sequestrant is colesevelam-HCl. In certain embodiments
the at least one proton pump inhibitor is omeprazole and the at
least one bile acid sequestrant is colestipol. In certain
embodiments the at least one proton pump inhibitor is esomeprazole
and the at least one bile acid sequestrant is cholestyramine. In
certain embodiments the at least one proton pump inhibitor is
esomeprazole and the at least one bile acid sequestrant is
colesevelam. In certain embodiments the at least one proton pump
inhibitor is esomeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is esomeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is lansoprazole and the at least one bile
acid sequestrant is cholestyramine. In certain embodiments the at
least one proton pump inhibitor is lansoprazole and the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one proton pump inhibitor is lansoprazole and the at
least one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is lansoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the at least one proton pump inhibitor is
pantoprazole and the at least one bile acid sequestrant is
cholestyramine. In certain embodiments the at least one proton pump
inhibitor is pantoprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is pantoprazole and the at least one bile
acid sequestrant is colesevelam-HCl. In certain embodiments the at
least one proton pump inhibitor is pantoprazole and the at least
one bile acid sequestrant is colestipol. In certain embodiments the
at least one proton pump inhibitor is rabeprazole and the at least
one bile acid sequestrant is cholestyramine. In certain embodiments
the at least one proton pump inhibitor is rabeprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is rabeprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
rabeprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is tenatoprazole and the at least one
bile acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is tenatoprazole and the at least
one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is tenatoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the dosage unit and daily dose are equivalent.
In various embodiments, the dosage unit is administered with food
at anytime of the day, without food at anytime of the day, with
food after an overnight fast (e.g. with breakfast), at bedtime
after a low fat snack. In various embodiments, the dosage unit is
administered once a day, twice a day, three times a day, four times
a day. The dosage unit can optionally comprise other agents such as
at least one antacid, at least one histamine Hz-receptor
antagonist, or combinations thereof.
In certain embodiments, the dosage unit comprises at least about or
less than about 5 mg of at least one proton pump inhibitor and at
least about or less than about 0.2 g, at least about or less than
about 0.4 g, at least about or less than about 0.6 g, at least
about or less than about 0.8 g, at least about or less than about 1
g, at least about or less than about 1.2 g, at least about or less
than about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 10 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 15 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 20 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 25 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 30 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 35 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 40 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 45 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 50 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 55 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 60 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 65 mg of at least one proton pump inhibitor and at least
about or less than about 0.2 g, at least about or less than about
0.4 g, at least about or less than about 0.6 g, at least about or
less than about 0.8 g, at least about or less than about 1 g, at
least about or less than about 1.2 g, at least about or less than
about 1.4 g, at least about or less than about 1.6 g, at least
about or less than about 1.8 g, at least about or less than about 2
g, at least about or less than about 2.2 g, at least about or less
than about 2.4 g, at least about or less than about 2.6 g, at least
about or less than about 2.8 g, at least about or less than about 3
g, at least about or less than about 3.2 g, at least about or less
than about 3.4 g, at least about or less than about 3.6 g, at least
about or less than about 3.8 g, at least about or less than about 4
g, at least about or less than about 4.2 g, at least about or less
than about 4.4 g, at least about or less than about 4.6 g, at least
about or less than about 4.8 g, at least about or less than about 5
g, at least about or less than about 5.2 g, at least about or less
than about 5.4 g, at least about or less than about 5.6 g, at least
about or less than about 5.8 g, or at least about or less than
about 6 g of at least one
bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 70 mg of at least one
proton pump inhibitor and at least about or less than about 0.2 g,
at least about or less than about 0.4 g, at least about or less
than about 0.6 g, at least about or less than about 0.8 g, at least
about or less than about 1 g, at least about or less than about 1.2
g, at least about or less than about 1.4 g, at least about or less
than about 1.6 g, at least about or less than about 1.8 g, at least
about or less than about 2 g, at least about or less than about 2.2
g, at least about or less than about 2.4 g, at least about or less
than about 2.6 g, at least about or less than about 2.8 g, at least
about or less than about 3 g, at least about or less than about 3.2
g, at least about or less than about 3.4 g, at least about or less
than about 3.6 g, at least about or less than about 3.8 g, at least
about or less than about 4 g, at least about or less than about 4.2
g, at least about or less than about 4.4 g, at least about or less
than about 4.6 g, at least about or less than about 4.8 g, at least
about or less than about 5 g, at least about or less than about 5.2
g, at least about or less than about 5.4 g, at least about or less
than about 5.6 g, at least about or less than about 5.8 g, or at
least about or less than about 6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 75 mg of at least one proton pump
inhibitor and at least about or less than about 0.2 g, at least
about or less than about 0.4 g, at least about or less than about
0.6 g, at least about or less than about 0.8 g, at least about or
less than about 1 g, at least about or less than about 1.2 g, at
least about or less than about 1.4 g, at least about or less than
about 1.6 g, at least about or less than about 1.8 g, at least
about or less than about 2 g, at least about or less than about 2.2
g, at least about or less than about 2.4 g, at least about or less
than about 2.6 g, at least about or less than about 2.8 g, at least
about or less than about 3 g, at least about or less than about 3.2
g, at least about or less than about 3.4 g, at least about or less
than about 3.6 g, at least about or less than about 3.8 g, at least
about or less than about 4 g, at least about or less than about 4.2
g, at least about or less than about 4.4 g, at least about or less
than about 4.6 g, at least about or less than about 4.8 g, at least
about or less than about 5 g, at least about or less than about 5.2
g, at least about or less than about 5.4 g, at least about or less
than about 5.6 g, at least about or less than about 5.8 g, or at
least about or less than about 6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 80 mg of at least one proton pump
inhibitor and at least about or less than about 0.2 g, at least
about or less than about 0.4 g, at least about or less than about
0.6 g, at least about or less than about 0.8 g, at least about or
less than about 1 g, at least about or less than about 1.2 g, at
least about or less than about 1.4 g, at least about or less than
about 1.6 g, at least about or less than about 1.8 g, at least
about or less than about 2 g, at least about or less than about 2.2
g, at least about or less than about 2.4 g, at least about or less
than about 2.6 g, at least about or less than about 2.8 g, at least
about or less than about 3 g, at least about or less than about 3.2
g, at least about or less than about 3.4 g, at least about or less
than about 3.6 g, at least about or less than about 3.8 g, at least
about or less than about 4 g, at least about or less than about 4.2
g, at least about or less than about 4.4 g, at least about or less
than about 4.6 g, at least about or less than about 4.8 g, at least
about or less than about 5 g, at least about or less than about 5.2
g, at least about or less than about 5.4 g, at least about or less
than about 5.6 g, at least about or less than about 5.8 g, or at
least about or less than about 6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 85 mg of at least one proton pump
inhibitor and at least about or less than about 0.2 g, at least
about or less than about 0.4 g, at least about or less than about
0.6 g, at least about or less than about 0.8 g, at least about or
less than about 1 g, at least about or less than about 1.2 g, at
least about or less than about 1.4 g, at least about or less than
about 1.6 g, at least about or less than about 1.8 g, at least
about or less than about 2 g, at least about or less than about 2.2
g, at least about or less than about 2.4 g, at least about or less
than about 2.6 g, at least about or less than about 2.8 g, at least
about or less than about 3 g, at least about or less than about 3.2
g, at least about or less than about 3.4 g, at least about or less
than about 3.6 g, at least about or less than about 3.8 g, at least
about or less than about 4 g, at least about or less than about 4.2
g, at least about or less than about 4.4 g, at least about or less
than about 4.6 g, at least about or less than about 4.8 g, at least
about or less than about 5 g, at least about or less than about 5.2
g, at least about or less than about 5.4 g, at least about or less
than about 5.6 g, at least about or less than about 5.8 g, or at
least about or less than about 6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 90 mg of at least one proton pump
inhibitor and at least about or less than about 0.2 g, at least
about or less than about 0.4 g, at least about or less than about
0.6 g, at least about or less than about 0.8 g, at least about or
less than about 1 g, at least about or less than about 1.2 g, at
least about or less than about 1.4 g, at least about or less than
about 1.6 g, at least about or less than about 1.8 g, at least
about or less than about 2 g, at least about or less than about 2.2
g, at least about or less than about 2.4 g, at least about or less
than about 2.6 g, at least about or less than about 2.8 g, at least
about or less than about 3 g, at least about or less than about 3.2
g, at least about or less than about 3.4 g, at least about or less
than about 3.6 g, at least about or less than about 3.8 g, at least
about or less than about 4 g, at least about or less than about 4.2
g, at least about or less than about 4.4 g, at least about or less
than about 4.6 g, at least about or less than about 4.8 g, at least
about or less than about 5 g, at least about or less than about 5.2
g, at least about or less than about 5.4 g, at least about or less
than about 5.6 g, at least about or less than about 5.8 g, or at
least about or less than about 6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 95 mg of at least one proton pump
inhibitor and at least about or less than about 0.2 g, at least
about or less than about 0.4 g, at least about or less than about
0.6 g, at least about or less than about 0.8 g, at least about or
less than about 1 g, at least about or less than about 1.2 g, at
least about or less than about 1.4 g, at least about or less than
about 1.6 g, at least about or less than about 1.8 g, at least
about or less than about 2 g, at least about or less than about 2.2
g, at least about or less than about 2.4 g, at least about or less
than about 2.6 g, at least about or less than about 2.8 g, at least
about or less than about 3 g, at least about or less than about 3.2
g, at least about or less than about 3.4 g, at least about or less
than about 3.6 g, at least about or less than about 3.8 g, at least
about or less than about 4 g, at least about or less than about 4.2
g, at least about or less than about 4.4 g, at least about or less
than about 4.6 g, at least about or less than about 4.8 g, at least
about or less than about 5 g, at least about or less than about 5.2
g, at least about or less than about 5.4 g, at least about or less
than about 5.6 g, at least about or less than about 5.8 g, or at
least about or less than about 6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 100 mg of at least one proton pump
inhibitor and at least about or less than about 0.2 g, at least
about or less than about 0.4 g, at least about or less than about
0.6 g, at least about or less than about 0.8 g, at least about or
less than about 1 g, at least about or less than about 1.2 g, at
least about or less than about 1.4 g, at least about or less than
about 1.6 g, at least about or less than about 1.8 g, at least
about or less than about 2 g, at least about or less than about 2.2
g, at least about or less than about 2.4 g, at least about or less
than about 2.6 g, at least about or less than about 2.8 g, at least
about or less than about 3 g, at least about or less than about 3.2
g, at least about or less than about 3.4 g, at least about or less
than about 3.6 g, at least about or less than about 3.8 g, at least
about or less than about 4 g, at least about or less than about 4.2
g, at least about or less than about 4.4 g, at least about or less
than about 4.6 g, at least about or less than about 4.8 g, at least
about or less than about 5 g, at least about or less than about 5.2
g, at least about or less than about 5.4 g, at least about or less
than about 5.6 g, at least about or less than about 5.8 g, or at
least about or less than about 6 g of at least one bile acid
sequestrant. In certain embodiments the at least one proton pump
inhibitor is omeprazole. In certain embodiments the at least one
proton pump inhibitor is esomeprazole. In certain embodiments the
at least one proton pump inhibitor is lansoprazole. In certain
embodiments the at least one proton pump inhibitor is pantoprazole.
In certain embodiments the at least one proton pump inhibitor is
rabeprazole. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole. In certain embodiments the at least one
bile acid sequestrant is cholestyramine. In certain embodiments the
at least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one bile acid sequestrant is
colesevelam-HCl. In certain embodiments the at least one bile acid
sequestrant is colestipol. In certain embodiments the at least one
proton pump inhibitor is omeprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is omeprazole and the at least one bile
acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is omeprazole and the at least one
bile acid sequestrant is colesevelam-HCl. In certain embodiments
the at least one proton pump inhibitor is omeprazole and the at
least one bile acid sequestrant is colestipol. In certain
embodiments the at least one proton pump inhibitor is esomeprazole
and the at least one bile acid sequestrant is cholestyramine. In
certain embodiments the at least one proton pump inhibitor is
esomeprazole and the at least one bile acid sequestrant is
colesevelam. In certain embodiments the at least one proton pump
inhibitor is esomeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is esomeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is lansoprazole and the at least one bile
acid sequestrant is cholestyramine. In certain embodiments the at
least one proton pump inhibitor is lansoprazole and the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one proton pump inhibitor is lansoprazole and the at
least one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is lansoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the at least one proton pump inhibitor is
pantoprazole and the at least one bile acid sequestrant is
cholestyramine. In certain embodiments the at least one proton pump
inhibitor is pantoprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is pantoprazole and the at least one bile
acid sequestrant is colesevelam-HCl. In certain embodiments the at
least one proton pump inhibitor is pantoprazole and the at least
one bile acid sequestrant is colestipol. In certain embodiments the
at least one proton pump inhibitor is rabeprazole and the at least
one bile acid sequestrant is cholestyramine. In certain embodiments
the at least one proton pump inhibitor is rabeprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is rabeprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
rabeprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is tenatoprazole and the at least one
bile acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is tenatoprazole and the at least
one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is tenatoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the dosage unit and daily dose are equivalent.
In various embodiments, the dosage unit is administered with food
at anytime of the day, without food at anytime of the day, with
food after an overnight fast (e.g. with breakfast), at bedtime
after a low fat snack. In various embodiments, the dosage unit is
administered once a day, twice a day, three times a day, four times
a day. The dosage unit can optionally comprise other agents such as
at least one antacid, at least one histamine Hz-receptor
antagonist, or combinations thereof.
In certain embodiments, the dosage unit comprises at least about or
less than about 5 mg of at least one proton pump inhibitor and at
least about or less than about 0.1 g, at least about or less than
about 0.2 g, at least about or less than about 0.3 g, at least
about or less than about 0.4 g, at least about or less than about
0.5 g, at least about or less than about 0.6 g, at least about or
less than about 0.7 g, at least about or less than about 0.8 g, at
least about or less than about 0.9 g, at least about or less than
about 1 g, at least about or less than about 1.1 g, at least about
or less than about 1.2 g, at least about or less than about 1.3 g,
at least about or less than about 1.4 g, at least about or less
than about 1.5 g, at least about or less than about 1.6 g, at least
about or less than about 1.7 g, at least about or less than about
1.8 g, at least about or less than about 1.9 g, at least about or
less than about 2 g, at least about or less than about 2.1 g, at
least about or less than about 2.2 g, at least about or less than
about 2.3 g, at least about or less than about 2.4 g, at least
about or less than about 2.5 g, at least about or less than about
2.6 g, at least about or less than about 2.7 g, at least about or
less than about 2.8 g, at least about or less than about 2.9 g, or
at least about or less than about 3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 10 mg of at least one proton pump
inhibitor and at least about or less than about 0.1 g, at least
about or less than about 0.2 g, at least about or less than about
0.3 g, at least about or less than about 0.4 g, at least about or
less than about 0.5 g, at least about or less than about 0.6 g, at
least about or less than about 0.7 g, at least about or less than
about 0.8 g, at least about or less than about 0.9 g, at least
about or less than about 1 g, at least about or less than about 1.1
g, at least about or less than about 1.2 g, at least about or less
than about 1.3 g, at least about or less than about 1.4 g, at least
about or less than about 1.5 g, at least about or less than about
1.6 g, at least about or less than about 1.7 g, at least about or
less than about 1.8 g, at least about or less than about 1.9 g, at
least about or less than about 2 g, at least about or less than
about 2.1 g, at least about or less than about 2.2 g, at least
about or less than about 2.3 g, at least about or less than about
2.4 g, at least about or less than about 2.5 g, at least about or
less than about 2.6 g, at least about or less than about 2.7 g, at
least about or less than about 2.8 g, at least about or less than
about 2.9 g, or at least about or less than about 3 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 5 mg of at least one
proton pump inhibitor and at least about or less than about 0.1 g,
at least about or less than about 0.2 g, at least about or less
than about 0.3 g, at least about or less than about 0.4 g, at least
about or less than about 0.5 g, at least about or less than about
0.6 g, at least about or less than about 0.7 g, at least about or
less than about 0.8 g, at least about or less than about 0.9 g, at
least about or less than about 1 g, at least about or less than
about 1.1 g, at least about or less than about 1.2 g, at least
about or less than about 1.3 g, at least about or less than about
1.4 g, at least about or less than about 1.5 g, at least about or
less than about 1.6 g, at least about or less than about 1.7 g, at
least about or less than about 1.8 g, at least about or less than
about 1.9 g, at least about or less than about 2 g, at least about
or less than about 2.1 g, at least about or less than about 2.2 g,
at least about or less than about 2.3 g, at least about or less
than about 2.4 g, at least about or less than about 2.5 g, at least
about or less than about 2.6 g, at least about or less than about
2.7 g, at least about or less than about 2.8 g, at least about or
less than about 2.9 g, or at least about or less than about 3 g of
at least one bile acid sequestrant. In certain embodiments, the
dosage unit comprises at least about or less than about 15 mg of at
least one proton pump inhibitor and at least about or less than
about 0.1 g, at least about or less than about 0.2 g, at least
about or less than about 0.3 g, at least about or less than about
0.4 g, at least about or less than about 0.5 g, at least about or
less than about 0.6 g, at least about or less than about 0.7 g, at
least about or less than about 0.8 g, at least about or less than
about 0.9 g, at least about or less than about 1 g, at least about
or less than about 1.1 g, at least about or less than about 1.2 g,
at least about or less than about 1.3 g, at least about or less
than about 1.4 g, at least about or less than about 1.5 g, at least
about or less than about 1.6 g, at least about or less than about
1.7 g, at least about or less than about 1.8 g, at least about or
less than about 1.9 g, at least about or less than about 2 g, at
least about or less than about 2.1 g, at least about or less than
about 2.2 g, at least about or less than about 2.3 g, at least
about or less than about 2.4 g, at least about or less than about
2.5 g, at least about or less than about 2.6 g, at least about or
less than about 2.7 g, at least about or less than about 2.8 g, at
least about or less than about 2.9 g, or at least about or less
than about 3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 20 mg of at least one proton pump inhibitor and at least
about or less than about 0.1 g, at least about or less than about
0.2 g, at least about or less than about 0.3 g, at least about or
less than about 0.4 g, at least about or less than about 0.5 g, at
least about or less than about 0.6 g, at least about or less than
about 0.7 g, at least about or less than about 0.8 g, at least
about or less than about 0.9 g, at least about or less than about 1
g, at least about or less than about 1.1 g, at least about or less
than about 1.2 g, at least about or less than about 1.3 g, at least
about or less than about 1.4 g, at least about or less than about
1.5 g, at least about or less than about 1.6 g, at least about or
less than about 1.7 g, at least about or less than about 1.8 g, at
least about or less than about 1.9 g, at least about or less than
about 2 g, at least about or less than about 2.1 g, at least about
or less than about 2.2 g, at least about or less than about 2.3 g,
at least about or less than about 2.4 g, at least about or less
than about 2.5 g, at least about or less than about 2.6 g, at least
about or less than about 2.7 g, at least about or less than about
2.8 g, at least about or less than about 2.9 g, or at least about
or less than about 3 g of at least one bile acid sequestrant. In
certain embodiments, the dosage unit comprises at least about or
less than about 25 mg of at least one proton pump inhibitor and at
least about or less than about 0.1 g, at least about or less than
about 0.2 g, at least about or less than about 0.3 g, at least
about or less than about 0.4 g, at least about or less than about
0.5 g, at least about or less than about 0.6 g, at least about or
less than about 0.7 g, at least about or less than about 0.8 g, at
least about or less than about 0.9 g, at least about or less than
about 1 g, at least about or less than about 1.1 g, at least about
or less than about 1.2 g, at least about or less than about 1.3 g,
at least about or less than about 1.4 g, at least about or less
than about 1.5 g, at least about or less than about 1.6 g, at least
about or less than about 1.7 g, at least about or less than about
1.8 g, at least about or less than about 1.9 g, at least about or
less than about 2 g, at least about or less than about 2.1 g, at
least about or less than about 2.2 g, at least about or less than
about 2.3 g, at least about or less than about 2.4 g, at least
about or less than about 2.5 g, at least about or less than about
2.6 g, at least about or less than about 2.7 g, at least about or
less than about 2.8 g, at least about or less than about 2.9 g, or
at least about or less than about 3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 30 mg of at least one proton pump
inhibitor and at least about or less than about 0.1 g, at least
about or less than about 0.2 g, at least about or less than about
0.3 g, at least about or less than about 0.4 g, at least about or
less than about 0.5 g, at least about or less than about 0.6 g, at
least about or less than about 0.7 g, at least about or less than
about 0.8 g, at least about or less than about 0.9 g, at least
about or less than about 1 g, at least about or less than about 1.1
g, at least about or less than about 1.2 g, at least about or less
than about 1.3 g, at least about or less than about 1.4 g, at least
about or less than about 1.5 g, at least about or less than about
1.6 g, at least about or less than about 1.7 g, at least about or
less than about 1.8 g, at least about or less than about 1.9 g, at
least about or less than about 2 g, at least about or less than
about 2.1 g, at least about or less than about 2.2 g, at least
about or less than about 2.3 g, at least about or less than about
2.4 g, at least about or less than about 2.5 g, at least about or
less than about 2.6 g, at least about or less than about 2.7 g, at
least about or less than about 2.8 g, at least about or less than
about 2.9 g, or at least about or less than about 3 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 35 mg of at least one
proton pump inhibitor and at least about or less than about 0.1 g,
at least about or less than about 0.2 g, at least about or less
than about 0.3 g, at least about or less than about 0.4 g, at least
about or less than about 0.5 g, at least about or less than about
0.6 g, at least about or less than about 0.7 g, at least about or
less than about 0.8 g, at least about or less than about 0.9 g, at
least about or less than about 1 g, at least about or less than
about 1.1 g, at least about or less than about 1.2 g, at least
about or less than about 1.3 g, at least about or less than about
1.4 g, at least about or less than about 1.5 g, at least about or
less than about 1.6 g, at least about or less than about 1.7 g, at
least about or less than about 1.8 g, at least about or less than
about 1.9 g, at least about or less than about 2 g, at least about
or less than about 2.1 g, at least about or less than about 2.2 g,
at least about or less than about 2.3 g, at least about or less
than about 2.4 g, at least about or less than about 2.5 g, at least
about or less than about 2.6 g, at least about or less than about
2.7 g, at least about or less than about 2.8 g, at least about or
less than about 2.9 g, or at least about or less than about 3 g of
at least one bile acid sequestrant. In certain embodiments, the
dosage unit comprises at least about or less than about 40 mg of at
least one proton pump inhibitor and at least about or less than
about 0.1 g, at least about or less than about 0.2 g, at least
about or less than about 0.3 g, at least about or less than about
0.4 g, at least about or less than about 0.5 g, at least about or
less than about 0.6 g, at least about or less than about 0.7 g, at
least about or less than about 0.8 g, at least about or less than
about 0.9 g, at least about or less than about 1 g, at least about
or less than about 1.1 g, at least about or less than about 1.2 g,
at least about or less than about 1.3 g, at least about or less
than about 1.4 g, at least about or less than about 1.5 g, at least
about or less than about 1.6 g, at least about or less than about
1.7 g, at least about or less than about 1.8 g, at least about or
less than about 1.9 g, at least about or less than about 2 g, at
least about or less than about 2.1 g, at least about or less than
about 2.2 g, at least about or less than about 2.3 g, at least
about or less than about 2.4 g, at least about or less than about
2.5 g, at least about or less than about 2.6 g, at least about or
less than about 2.7 g, at least about or less than about 2.8 g, at
least about or less than about 2.9 g, or at least about or less
than about 3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 45 mg of at least one proton pump inhibitor and at least
about or less than about 0.1 g, at least about or less than about
0.2 g, at least about or less than about 0.3 g, at least about or
less than about 0.4 g, at least about or less than about 0.5 g, at
least about or less than about 0.6 g, at least about or less than
about 0.7 g, at least about or less than about 0.8 g, at least
about or less than about 0.9 g, at least about or less than about 1
g, at least about or less than about 1.1 g, at least about or less
than about 1.2 g, at least about or less than about 1.3 g, at least
about or less than about 1.4 g, at least about or less than about
1.5 g, at least about or less than about 1.6 g, at least about or
less than about 1.7 g, at least about or less than about 1.8 g, at
least about or less than about 1.9 g, at least about or less than
about 2 g, at least about or less than about 2.1 g, at least about
or less than about 2.2 g, at least about or less than about 2.3 g,
at least about or less than about 2.4 g, at least about or less
than about 2.5 g, at least about or less than about 2.6 g, at least
about or less than about 2.7 g, at least about or less than about
2.8 g, at least about or less than about 2.9 g, or at least about
or less than about 3 g of at least one bile acid sequestrant. In
certain embodiments, the dosage unit comprises at least about or
less than about 50 mg of at least one proton pump inhibitor and at
least about or less than about 0.1 g, at least about or less than
about 0.2 g, at least about or less than about 0.3 g, at least
about or less than about 0.4 g, at least about or less than about
0.5 g, at least about or less than about 0.6 g, at least about or
less than about 0.7 g, at least about or less than about 0.8 g, at
least about or less than about 0.9 g, at least about or less than
about 1 g, at least about or less than about 1.1 g, at least about
or less than about 1.2 g, at least about or less than about 1.3 g,
at least about or less than about 1.4 g, at least about or less
than about 1.5 g, at least about or less than about 1.6 g, at least
about or less than about 1.7 g, at least about or less than about
1.8 g, at least about or less than about 1.9 g, at least about or
less than about 2 g, at least about or less than about 2.1 g, at
least about or less than about 2.2 g, at least about or less than
about 2.3 g, at least about or less than about 2.4 g, at least
about or less than about 2.5 g, at least about or less than about
2.6 g, at least about or less than about 2.7 g, at least about or
less than about 2.8 g, at least about or less than about 2.9 g, or
at least about or less than about 3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 55 mg of at least one proton pump
inhibitor and at least about or less than about 0.1 g, at least
about or less than about 0.2 g, at least about or less than about
0.3 g, at least about or less than about 0.4 g, at least about or
less than about 0.5 g, at least about or less than about 0.6 g, at
least about or less than about 0.7 g, at least about or less than
about 0.8 g, at least about or less than about 0.9 g, at least
about or less than about 1 g, at least about or less than about 1.1
g, at least about or less than about 1.2 g, at least about or less
than about 1.3 g, at least about or less than about 1.4 g, at least
about or less than about 1.5 g, at least about or less than about
1.6 g, at least about or less than about 1.7 g, at least about or
less than about 1.8 g, at least about or less than about 1.9 g, at
least about or less than about 2 g, at least about or less than
about 2.1 g, at least about or less than about 2.2 g, at least
about or less than about 2.3 g, at least about or less than about
2.4 g, at least about or less than about 2.5 g, at least about or
less than about 2.6 g, at least about or less than about 2.7 g, at
least about or less than about 2.8 g, at least about or less than
about 2.9 g, or at least about or less than about 3 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 60 mg of at least one
proton pump inhibitor and at least about or less than about 0.1 g,
at least about or less than about 0.2 g, at least about or less
than about 0.3 g, at least about or less than about 0.4 g, at least
about or less than about 0.5 g, at least about or less than about
0.6 g, at least about or less than about 0.7 g, at least about or
less than about 0.8 g, at least about or less than about 0.9 g, at
least about or less than about 1 g, at least about or less than
about 1.1 g, at least about or less than about 1.2 g, at least
about or less than about 1.3 g, at least about or less than about
1.4 g, at least about or less than about 1.5 g, at least about or
less than about 1.6 g, at least about or less than about 1.7 g, at
least about or less than about 1.8 g, at least about or less than
about 1.9 g, at least about or less than about 2 g, at least about
or less than about 2.1 g, at least about or less than about 2.2 g,
at least about or less than about 2.3 g, at least about or less
than about 2.4 g, at least about or less than about 2.5 g, at least
about or less than about 2.6 g, at least about or less than about
2.7 g, at least
about or less than about 2.8 g, at least about or less than about
2.9 g, or at least about or less than about 3 g of at least one
bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 65 mg of at least one
proton pump inhibitor and at least about or less than about 0.1 g,
at least about or less than about 0.2 g, at least about or less
than about 0.3 g, at least about or less than about 0.4 g, at least
about or less than about 0.5 g, at least about or less than about
0.6 g, at least about or less than about 0.7 g, at least about or
less than about 0.8 g, at least about or less than about 0.9 g, at
least about or less than about 1 g, at least about or less than
about 1.1 g, at least about or less than about 1.2 g, at least
about or less than about 1.3 g, at least about or less than about
1.4 g, at least about or less than about 1.5 g, at least about or
less than about 1.6 g, at least about or less than about 1.7 g, at
least about or less than about 1.8 g, at least about or less than
about 1.9 g, at least about or less than about 2 g, at least about
or less than about 2.1 g, at least about or less than about 2.2 g,
at least about or less than about 2.3 g, at least about or less
than about 2.4 g, at least about or less than about 2.5 g, at least
about or less than about 2.6 g, at least about or less than about
2.7 g, at least about or less than about 2.8 g, at least about or
less than about 2.9 g, or at least about or less than about 3 g of
at least one bile acid sequestrant. In certain embodiments, the
dosage unit comprises at least about or less than about 70 mg of at
least one proton pump inhibitor and at least about or less than
about 0.1 g, at least about or less than about 0.2 g, at least
about or less than about 0.3 g, at least about or less than about
0.4 g, at least about or less than about 0.5 g, at least about or
less than about 0.6 g, at least about or less than about 0.7 g, at
least about or less than about 0.8 g, at least about or less than
about 0.9 g, at least about or less than about 1 g, at least about
or less than about 1.1 g, at least about or less than about 1.2 g,
at least about or less than about 1.3 g, at least about or less
than about 1.4 g, at least about or less than about 1.5 g, at least
about or less than about 1.6 g, at least about or less than about
1.7 g, at least about or less than about 1.8 g, at least about or
less than about 1.9 g, at least about or less than about 2 g, at
least about or less than about 2.1 g, at least about or less than
about 2.2 g, at least about or less than about 2.3 g, at least
about or less than about 2.4 g, at least about or less than about
2.5 g, at least about or less than about 2.6 g, at least about or
less than about 2.7 g, at least about or less than about 2.8 g, at
least about or less than about 2.9 g, or at least about or less
than about 3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 75 mg of at least one proton pump inhibitor and at least
about or less than about 0.1 g, at least about or less than about
0.2 g, at least about or less than about 0.3 g, at least about or
less than about 0.4 g, at least about or less than about 0.5 g, at
least about or less than about 0.6 g, at least about or less than
about 0.7 g, at least about or less than about 0.8 g, at least
about or less than about 0.9 g, at least about or less than about 1
g, at least about or less than about 1.1 g, at least about or less
than about 1.2 g, at least about or less than about 1.3 g, at least
about or less than about 1.4 g, at least about or less than about
1.5 g, at least about or less than about 1.6 g, at least about or
less than about 1.7 g, at least about or less than about 1.8 g, at
least about or less than about 1.9 g, at least about or less than
about 2 g, at least about or less than about 2.1 g, at least about
or less than about 2.2 g, at least about or less than about 2.3 g,
at least about or less than about 2.4 g, at least about or less
than about 2.5 g, at least about or less than about 2.6 g, at least
about or less than about 2.7 g, at least about or less than about
2.8 g, at least about or less than about 2.9 g, or at least about
or less than about 3 g of at least one bile acid sequestrant. In
certain embodiments, the dosage unit comprises at least about or
less than about 80 mg of at least one proton pump inhibitor and at
least about or less than about 0.1 g, at least about or less than
about 0.2 g, at least about or less than about 0.3 g, at least
about or less than about 0.4 g, at least about or less than about
0.5 g, at least about or less than about 0.6 g, at least about or
less than about 0.7 g, at least about or less than about 0.8 g, at
least about or less than about 0.9 g, at least about or less than
about 1 g, at least about or less than about 1.1 g, at least about
or less than about 1.2 g, at least about or less than about 1.3 g,
at least about or less than about 1.4 g, at least about or less
than about 1.5 g, at least about or less than about 1.6 g, at least
about or less than about 1.7 g, at least about or less than about
1.8 g, at least about or less than about 1.9 g, at least about or
less than about 2 g, at least about or less than about 2.1 g, at
least about or less than about 2.2 g, at least about or less than
about 2.3 g, at least about or less than about 2.4 g, at least
about or less than about 2.5 g, at least about or less than about
2.6 g, at least about or less than about 2.7 g, at least about or
less than about 2.8 g, at least about or less than about 2.9 g, or
at least about or less than about 3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 85 mg of at least one proton pump
inhibitor and at least about or less than about 0.1 g, at least
about or less than about 0.2 g, at least about or less than about
0.3 g, at least about or less than about 0.4 g, at least about or
less than about 0.5 g, at least about or less than about 0.6 g, at
least about or less than about 0.7 g, at least about or less than
about 0.8 g, at least about or less than about 0.9 g, at least
about or less than about 1 g, at least about or less than about 1.1
g, at least about or less than about 1.2 g, at least about or less
than about 1.3 g, at least about or less than about 1.4 g, at least
about or less than about 1.5 g, at least about or less than about
1.6 g, at least about or less than about 1.7 g, at least about or
less than about 1.8 g, at least about or less than about 1.9 g, at
least about or less than about 2 g, at least about or less than
about 2.1 g, at least about or less than about 2.2 g, at least
about or less than about 2.3 g, at least about or less than about
2.4 g, at least about or less than about 2.5 g, at least about or
less than about 2.6 g, at least about or less than about 2.7 g, at
least about or less than about 2.8 g, at least about or less than
about 2.9 g, or at least about or less than about 3 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 90 mg of at least one
proton pump inhibitor and at least about or less than about 0.1 g,
at least about or less than about 0.2 g, at least about or less
than about 0.3 g, at least about or less than about 0.4 g, at least
about or less than about 0.5 g, at least about or less than about
0.6 g, at least about or less than about 0.7 g, at least about or
less than about 0.8 g, at least about or less than about 0.9 g, at
least about or less than about 1 g, at least about or less than
about 1.1 g, at least about or less than about 1.2 g, at least
about or less than about 1.3 g, at least about or less than about
1.4 g, at least about or less than about 1.5 g, at least about or
less than about 1.6 g, at least about or less than about 1.7 g, at
least about or less than about 1.8 g, at least about or less than
about 1.9 g, at least about or less than about 2 g, at least about
or less than about 2.1 g, at least about or less than about 2.2 g,
at least about or less than about 2.3 g, at least about or less
than about 2.4 g, at least about or less than about 2.5 g, at least
about or less than about 2.6 g, at least about or less than about
2.7 g, at least about or less than about 2.8 g, at least about or
less than about 2.9 g, or at least about or less than about 3 g of
at least one bile acid sequestrant. In certain embodiments, the
dosage unit comprises at least about or less than about 95 mg of at
least one proton pump inhibitor and at least about or less than
about 0.1 g, at least about or less than about 0.2 g, at least
about or less than about 0.3 g, at least about or less than about
0.4 g, at least about or less than about 0.5 g, at least about or
less than about 0.6 g, at least about or less than about 0.7 g, at
least about or less than about 0.8 g, at least about or less than
about 0.9 g, at least about or less than about 1 g, at least about
or less than about 1.1 g, at least about or less than about 1.2 g,
at least about or less than about 1.3 g, at least about or less
than about 1.4 g, at least about or less than about 1.5 g, at least
about or less than about 1.6 g, at least about or less than about
1.7 g, at least about or less than about 1.8 g, at least about or
less than about 1.9 g, at least about or less than about 2 g, at
least about or less than about 2.1 g, at least about or less than
about 2.2 g, at least about or less than about 2.3 g, at least
about or less than about 2.4 g, at least about or less than about
2.5 g, at least about or less than about 2.6 g, at least about or
less than about 2.7 g, at least about or less than about 2.8 g, at
least about or less than about 2.9 g, or at least about or less
than about 3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 100 mg of at least one proton pump inhibitor and at least
about or less than about 0.1 g, at least about or less than about
0.2 g, at least about or less than about 0.3 g, at least about or
less than about 0.4 g, at least about or less than about 0.5 g, at
least about or less than about 0.6 g, at least about or less than
about 0.7 g, at least about or less than about 0.8 g, at least
about or less than about 0.9 g, at least about or less than about 1
g, at least about or less than about 1.1 g, at least about or less
than about 1.2 g, at least about or less than about 1.3 g, at least
about or less than about 1.4 g, at least about or less than about
1.5 g, at least about or less than about 1.6 g, at least about or
less than about 1.7 g, at least about or less than about 1.8 g, at
least about or less than about 1.9 g, at least about or less than
about 2 g, at least about or less than about 2.1 g, at least about
or less than about 2.2 g, at least about or less than about 2.3 g,
at least about or less than about 2.4 g, at least about or less
than about 2.5 g, at least about or less than about 2.6 g, at least
about or less than about 2.7 g, at least about or less than about
2.8 g, at least about or less than about 2.9 g, or at least about
or less than about 3 g of at least one bile acid sequestrant. In
certain embodiments the at least one proton pump inhibitor is
omeprazole. In certain embodiments the at least one proton pump
inhibitor is esomeprazole. In certain embodiments the at least one
proton pump inhibitor is lansoprazole. In certain embodiments the
at least one proton pump inhibitor is pantoprazole. In certain
embodiments the at least one proton pump inhibitor is rabeprazole.
In certain embodiments the at least one proton pump inhibitor is
tenatoprazole. In certain embodiments the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is omeprazole and the at least one bile acid sequestrant
is cholestyramine. In certain embodiments the at least one proton
pump inhibitor is omeprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is omeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is omeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is esomeprazole and the at least one bile
acid sequestrant is cholestyramine. In certain embodiments the at
least one proton pump inhibitor is esomeprazole and the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one proton pump inhibitor is esomeprazole and the at
least one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is esomeprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the at least one proton pump inhibitor is
lansoprazole and the at least one bile acid sequestrant is
cholestyramine. In certain embodiments the at least one proton pump
inhibitor is lansoprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is lansoprazole and the at least one bile
acid sequestrant is colesevelam-HCl. In certain embodiments the at
least one proton pump inhibitor is lansoprazole and the at least
one bile acid sequestrant is colestipol. In certain embodiments the
at least one proton pump inhibitor is pantoprazole and the at least
one bile acid sequestrant is cholestyramine. In certain embodiments
the at least one proton pump inhibitor is pantoprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is pantoprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
pantoprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is rabeprazole and the at least one bile acid sequestrant
is cholestyramine. In certain embodiments the at least one proton
pump inhibitor is rabeprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is rabeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is rabeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is tenatoprazole and the at least one
bile acid sequestrant is cholestyramine. In certain embodiments the
at least one proton pump inhibitor is tenatoprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is tenatoprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
tenatoprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the dosage unit and daily dose
are equivalent. In various embodiments, the dosage unit is
administered with food at anytime of the day, without food at
anytime of the day, with food after an overnight fast (e.g. with
breakfast), at bedtime after a low fat snack. In various
embodiments, the dosage unit is administered once a day, twice a
day, three times a day, four times a day. The dosage unit can
optionally comprise other agents such as at least one antacid, at
least one histamine Hz-receptor antagonist, or combinations
thereof.
In certain embodiments, the dosage unit comprises at least about or
less than about 5 mg of at least one proton pump inhibitor and at
least about or less than about 0.02 g, at least about or less than
about 0.04 g, at least about or less than about 0.06 g, at least
about or less than about 0.08 g, at least about or less than about
0.1 g, at least about or less than about 0.12 g, at least about or
less than about 0.14 g, at least about or less than about 0.16 g,
at least about or less than about 0.18 g, at least about or less
than about 0.2 g, at least about or less than about 0.22 g, at
least about or less than about 0.24 g, at least about or less than
about 0.26 g, at least about or less than about 0.28 g, at least
about or less than about 0.3 g, at least about or less than about
0.32 g, at least about or less than about 0.34 g, at least about or
less than about 0.36 g, at least about or less than about 0.38 g,
at least about or less than about 0.4 g, at least about or less
than about 0.42 g, at least about or less than about 0.44 g, at
least about or less than about 0.46 g, at least about or less than
about 0.48 g, at least about or less than about 0.5 g, at least
about or less than about 0.52 g, at least about or less than about
0.54 g, at least about or less than about 0.56 g, at least about or
less than about 0.58 g, or at least about or less than about 0.6 g
of at least one bile acid sequestrant. In certain embodiments, the
dosage unit comprises at least about or less than about 10 mg of at
least one proton pump inhibitor and at least about or less than
about 0.02 g, at least about or less than about 0.04 g, at least
about or less than about 0.06 g, at least about or less than about
0.08 g, at least about or less than about 0.1 g, at least about or
less than about 0.12 g, at least about or less than about 0.14 g,
at least about or less than about 0.16 g, at least about or less
than about 0.18 g, at least about or less than about 0.2 g, at
least about or less than about 0.22 g, at least about or less than
about 0.24 g, at least about or less than about 0.26 g, at least
about or less than about 0.28 g, at least about or less than about
0.3 g, at least about or less than about 0.32 g, at least about or
less than about 0.34 g, at least about or less than about 0.36 g,
at least about or less than about 0.38 g, at least about or less
than about 0.4 g, at least about or less than about 0.42 g, at
least about or less than about 0.44 g, at least about or less than
about 0.46 g, at least about or less than about 0.48 g, at least
about or less than about 0.5 g, at least about or less than about
0.52 g, at least about or less than about 0.54 g, at least about or
less than about 0.56 g, at least about or less than about 0.58 g,
or at least about or less than about 0.6 g of at least one bile
acid sequestrant. In certain embodiments, the dosage unit comprises
at least about or less than about 15 mg of at least one proton pump
inhibitor and at least about or less than about 0.02 g, at least
about or less than about 0.04 g, at least about or less than about
0.06 g, at least about or less than about 0.08 g, at least about or
less than about 0.1 g, at least about or less than about 0.12 g, at
least about or less than about 0.14 g, at least about or less than
about 0.16 g, at least about or less than about 0.18 g, at least
about or less than about 0.2 g, at least about or less than about
0.22 g, at least about or less than about 0.24 g, at least about or
less than about 0.26 g, at least about or less than about 0.28 g,
at least about or less than about 0.3 g, at least about or less
than about 0.32 g, at least about or less than about 0.34 g, at
least about or less than about 0.36 g, at least about or less than
about 0.38 g, at least about or less than about 0.4 g, at least
about or less than about 0.42 g, at least about or less than about
0.44 g, at least about or less than about 0.46 g, at least about or
less than about 0.48 g, at least about or less than about 0.5 g, at
least about or less than about 0.52 g, at least about or less than
about 0.54 g, at least about or less than about 0.56 g, at least
about or less than about 0.58 g, or at least about or less than
about 0.6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 20 mg of at least one proton pump inhibitor and at least
about or less than about 0.02 g, at least about or less than about
0.04 g, at least about or less than about 0.06 g, at least about or
less than about 0.08 g, at least about or less than about 0.1 g, at
least about or less than about 0.12 g, at least about or less than
about 0.14 g, at least about or less than about 0.16 g, at least
about or less than about 0.18 g, at least about or less than about
0.2 g, at least about or less than about 0.22 g, at least about or
less than about 0.24 g, at least about or less than about 0.26 g,
at least about or less than about 0.28 g, at least about or less
than about 0.3 g, at least about or less than about 0.32 g, at
least about or less than about 0.34 g, at least about or less than
about 0.36 g, at least about or less than about 0.38 g, at least
about or less than about 0.4 g, at least about or less than about
0.42 g, at least about or less than about 0.44 g, at least about or
less than about 0.46 g, at least about or less than about 0.48 g,
at least about or less than about 0.5 g, at least about or less
than about 0.52 g, at least about or less than about 0.54 g, at
least about or less than about 0.56 g, at least about or less than
about 0.58 g, or at least about or less than about 0.6 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 25 mg of at least
one proton pump inhibitor and at least about or less than about
0.02 g, at least about or less than about 0.04 g, at least about or
less than about 0.06 g, at least about or less than about 0.08 g,
at least about or less than about 0.1 g, at least about or less
than about 0.12 g, at least about or less than about 0.14 g, at
least about or less than about 0.16 g, at least about or less than
about 0.18 g, at least about or less than about 0.2 g, at least
about or less than about 0.22 g, at least about or less than about
0.24 g, at least about or less than about 0.26 g, at least about or
less than about 0.28 g, at least about or less than about 0.3 g, at
least about or less than about 0.32 g, at least about or less than
about 0.34 g, at least about or less than about 0.36 g, at least
about or less than about 0.38 g, at least about or less than about
0.4 g, at least about or less than about 0.42 g, at least about or
less than about 0.44 g, at least about or less than about 0.46 g,
at least about or less than about 0.48 g, at least about or less
than about 0.5 g, at least about or less than about 0.52 g, at
least about or less than about 0.54 g, at least about or less than
about 0.56 g, at least about or less than about 0.58 g, or at least
about or less than about 0.6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 30 mg of at least one proton pump
inhibitor and at least about or less than about 0.02 g, at least
about or less than about 0.04 g, at least about or less than about
0.06 g, at least about or less than about 0.08 g, at least about or
less than about 0.1 g, at least about or less than about 0.12 g, at
least about or less than about 0.14 g, at least about or less than
about 0.16 g, at least about or less than about 0.18 g, at least
about or less than about 0.2 g, at least about or less than about
0.22 g, at least about or less than about 0.24 g, at least about or
less than about 0.26 g, at least about or less than about 0.28 g,
at least about or less than about 0.3 g, at least about or less
than about 0.32 g, at least about or less than about 0.34 g, at
least about or less than about 0.36 g, at least about or less than
about 0.38 g, at least about or less than about 0.4 g, at least
about or less than about 0.42 g, at least about or less than about
0.44 g, at least about or less than about 0.46 g, at least about or
less than about 0.48 g, at least about or less than about 0.5 g, at
least about or less than about 0.52 g, at least about or less than
about 0.54 g, at least about or less than about 0.56 g, at least
about or less than about 0.58 g, or at least about or less than
about 0.6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 35 mg of at least one proton pump inhibitor and at least
about or less than about 0.02 g, at least about or less than about
0.04 g, at least about or less than about 0.06 g, at least about or
less than about 0.08 g, at least about or less than about 0.1 g, at
least about or less than about 0.12 g, at least about or less than
about 0.14 g, at least about or less than about 0.16 g, at least
about or less than about 0.18 g, at least about or less than about
0.2 g, at least about or less than about 0.22 g, at least about or
less than about 0.24 g, at least about or less than about 0.26 g,
at least about or less than about 0.28 g, at least about or less
than about 0.3 g, at least about or less than about 0.32 g, at
least about or less than about 0.34 g, at least about or less than
about 0.36 g, at least about or less than about 0.38 g, at least
about or less than about 0.4 g, at least about or less than about
0.42 g, at least about or less than about 0.44 g, at least about or
less than about 0.46 g, at least about or less than about 0.48 g,
at least about or less than about 0.5 g, at least about or less
than about 0.52 g, at least about or less than about 0.54 g, at
least about or less than about 0.56 g, at least about or less than
about 0.58 g, or at least about or less than about 0.6 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 40 mg of at least
one proton pump inhibitor and at least about or less than about
0.02 g, at least about or less than about 0.04 g, at least about or
less than about 0.06 g, at least about or less than about 0.08 g,
at least about or less than about 0.1 g, at least about or less
than about 0.12 g, at least about or less than about 0.14 g, at
least about or less than about 0.16 g, at least about or less than
about 0.18 g, at least about or less than about 0.2 g, at least
about or less than about 0.22 g, at least about or less than about
0.24 g, at least about or less than about 0.26 g, at least about or
less than about 0.28 g, at least about or less than about 0.3 g, at
least about or less than about 0.32 g, at least about or less than
about 0.34 g, at least about or less than about 0.36 g, at least
about or less than about 0.38 g, at least about or less than about
0.4 g, at least about or less than about 0.42 g, at least about or
less than about 0.44 g, at least about or less than about 0.46 g,
at least about or less than about 0.48 g, at least about or less
than about 0.5 g, at least about or less than about 0.52 g, at
least about or less than about 0.54 g, at least about or less than
about 0.56 g, at least about or less than about 0.58 g, or at least
about or less than about 0.6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 45 mg of at least one proton pump
inhibitor and at least about or less than about 0.02 g, at least
about or less than about 0.04 g, at least about or less than about
0.06 g, at least about or less than about 0.08 g, at least about or
less than about 0.1 g, at least about or less than about 0.12 g, at
least about or less than about 0.14 g, at least about or less than
about 0.16 g, at least about or less than about 0.18 g, at least
about or less than about 0.2 g, at least about or less than about
0.22 g, at least about or less than about 0.24 g, at least about or
less than about 0.26 g, at least about or less than about 0.28 g,
at least about or less than about 0.3 g, at least about or less
than about 0.32 g, at least about or less than about 0.34 g, at
least about or less than about 0.36 g, at least about or less than
about 0.38 g, at least about or less than about 0.4 g, at least
about or less than about 0.42 g, at least about or less than about
0.44 g, at least about or less than about 0.46 g, at least about or
less than about 0.48 g, at least about or less than about 0.5 g, at
least about or less than about 0.52 g, at least about or less than
about 0.54 g, at least about or less than about 0.56 g, at least
about or less than about 0.58 g, or at least about or less than
about 0.6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 50 mg of at least one proton pump inhibitor and at least
about or less than about 0.02 g, at least about or less than about
0.04 g, at least about or less than about 0.06 g, at least about or
less than about 0.08 g, at least about or less than about 0.1 g, at
least about or less than about 0.12 g, at least about or less than
about 0.14 g, at least about or less than about 0.16 g, at least
about or less than about 0.18 g, at least about or less than about
0.2 g, at least about or less than about 0.22 g, at least about or
less than about 0.24 g, at least about or less than about 0.26 g,
at least about or less than about 0.28 g, at least about or less
than about 0.3 g, at least about or less than about 0.32 g, at
least about or less than about 0.34 g, at least about or less than
about 0.36 g, at least about or less than about 0.38 g, at least
about or less than about 0.4 g, at least about or less than about
0.42 g, at least about or less than about 0.44 g, at least about or
less than about 0.46 g, at least about or less than about 0.48 g,
at least about or less than about 0.5 g, at least about or less
than about 0.52 g, at least about or less than about 0.54 g, at
least about or less than about 0.56 g, at least about or less than
about 0.58 g, or at least about or less than about 0.6 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 55 mg of at least
one proton pump inhibitor and at least about or less than about
0.02 g, at least about or less than about 0.04 g, at least about or
less than about 0.06 g, at least about or less than about 0.08 g,
at least about or less than about 0.1 g, at least about or less
than about 0.12 g, at least about or less than about 0.14 g, at
least about or less than about 0.16 g, at least about or less than
about 0.18 g, at least about or less than about 0.2 g, at least
about or less than about 0.22 g, at least about or less than about
0.24 g, at least about or less than about 0.26 g, at least about or
less than about 0.28 g, at least about or less than about 0.3 g, at
least about or less than about 0.32 g, at least about or less than
about 0.34 g, at least about or less than about 0.36 g, at least
about or less than about 0.38 g, at least about or less than about
0.4 g, at least about or less than about 0.42 g, at least about or
less than about 0.44 g, at least about or less than about 0.46 g,
at least about or less than about 0.48 g, at least about or less
than about 0.5 g, at least about or less than about 0.52 g, at
least about or less than about 0.54 g, at least about or less than
about 0.56 g, at least about or less than about 0.58 g, or at least
about or less than about 0.6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 60 mg of at least one proton pump
inhibitor and at least about or less than about 0.02 g, at least
about or less than about 0.04 g, at least about or less than about
0.06 g, at least about or less than about 0.08 g, at least about or
less than about 0.1 g, at least about or less than about 0.12 g, at
least about or less than about 0.14 g, at least about or less than
about 0.16 g, at least about or less than about 0.18 g, at least
about or less than about 0.2 g, at least about or less than about
0.22 g, at least about or less than about 0.24 g, at least about or
less than about 0.26 g, at least about or less than about 0.28 g,
at least about or less than about 0.3 g, at least about or less
than about 0.32 g, at least about or less than about 0.34 g, at
least about or less than about 0.36 g, at least about or less than
about 0.38 g, at least about or less than about 0.4 g, at least
about or less than about 0.42 g, at least about or less than about
0.44 g, at least about or less than about 0.46 g, at least about or
less than about 0.48 g, at least about or less than about 0.5 g, at
least about or less than about 0.52 g, at least about or less than
about 0.54 g, at least about or less than about 0.56 g, at least
about or less than about 0.58 g, or at least about or less than
about 0.6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 65 mg of at least one proton pump inhibitor and at least
about or less than about 0.02 g, at least about or less than about
0.04 g, at least about or less than about 0.06 g, at least about or
less than about 0.08 g, at least about or less than about 0.1 g, at
least about or less than about 0.12 g, at least about or less than
about 0.14 g, at least about or less than about 0.16 g, at least
about or less than about 0.18 g, at least about or less than about
0.2 g, at least about or less than about 0.22 g, at least about or
less than about 0.24 g, at least about or less than about 0.26 g,
at least about or less than about 0.28 g, at least about or less
than about 0.3 g, at least about or less than about 0.32 g,
at least about or less than about 0.34 g, at least about or less
than about 0.36 g, at least about or less than about 0.38 g, at
least about or less than about 0.4 g, at least about or less than
about 0.42 g, at least about or less than about 0.44 g, at least
about or less than about 0.46 g, at least about or less than about
0.48 g, at least about or less than about 0.5 g, at least about or
less than about 0.52 g, at least about or less than about 0.54 g,
at least about or less than about 0.56 g, at least about or less
than about 0.58 g, or at least about or less than about 0.6 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 70 mg of at least
one proton pump inhibitor and at least about or less than about
0.02 g, at least about or less than about 0.04 g, at least about or
less than about 0.06 g, at least about or less than about 0.08 g,
at least about or less than about 0.1 g, at least about or less
than about 0.12 g, at least about or less than about 0.14 g, at
least about or less than about 0.16 g, at least about or less than
about 0.18 g, at least about or less than about 0.2 g, at least
about or less than about 0.22 g, at least about or less than about
0.24 g, at least about or less than about 0.26 g, at least about or
less than about 0.28 g, at least about or less than about 0.3 g, at
least about or less than about 0.32 g, at least about or less than
about 0.34 g, at least about or less than about 0.36 g, at least
about or less than about 0.38 g, at least about or less than about
0.4 g, at least about or less than about 0.42 g, at least about or
less than about 0.44 g, at least about or less than about 0.46 g,
at least about or less than about 0.48 g, at least about or less
than about 0.5 g, at least about or less than about 0.52 g, at
least about or less than about 0.54 g, at least about or less than
about 0.56 g, at least about or less than about 0.58 g, or at least
about or less than about 0.6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 75 mg of at least one proton pump
inhibitor and at least about or less than about 0.02 g, at least
about or less than about 0.04 g, at least about or less than about
0.06 g, at least about or less than about 0.08 g, at least about or
less than about 0.1 g, at least about or less than about 0.12 g, at
least about or less than about 0.14 g, at least about or less than
about 0.16 g, at least about or less than about 0.18 g, at least
about or less than about 0.2 g, at least about or less than about
0.22 g, at least about or less than about 0.24 g, at least about or
less than about 0.26 g, at least about or less than about 0.28 g,
at least about or less than about 0.3 g, at least about or less
than about 0.32 g, at least about or less than about 0.34 g, at
least about or less than about 0.36 g, at least about or less than
about 0.38 g, at least about or less than about 0.4 g, at least
about or less than about 0.42 g, at least about or less than about
0.44 g, at least about or less than about 0.46 g, at least about or
less than about 0.48 g, at least about or less than about 0.5 g, at
least about or less than about 0.52 g, at least about or less than
about 0.54 g, at least about or less than about 0.56 g, at least
about or less than about 0.58 g, or at least about or less than
about 0.6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 80 mg of at least one proton pump inhibitor and at least
about or less than about 0.02 g, at least about or less than about
0.04 g, at least about or less than about 0.06 g, at least about or
less than about 0.08 g, at least about or less than about 0.1 g, at
least about or less than about 0.12 g, at least about or less than
about 0.14 g, at least about or less than about 0.16 g, at least
about or less than about 0.18 g, at least about or less than about
0.2 g, at least about or less than about 0.22 g, at least about or
less than about 0.24 g, at least about or less than about 0.26 g,
at least about or less than about 0.28 g, at least about or less
than about 0.3 g, at least about or less than about 0.32 g, at
least about or less than about 0.34 g, at least about or less than
about 0.36 g, at least about or less than about 0.38 g, at least
about or less than about 0.4 g, at least about or less than about
0.42 g, at least about or less than about 0.44 g, at least about or
less than about 0.46 g, at least about or less than about 0.48 g,
at least about or less than about 0.5 g, at least about or less
than about 0.52 g, at least about or less than about 0.54 g, at
least about or less than about 0.56 g, at least about or less than
about 0.58 g, or at least about or less than about 0.6 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 85 mg of at least
one proton pump inhibitor and at least about or less than about
0.02 g, at least about or less than about 0.04 g, at least about or
less than about 0.06 g, at least about or less than about 0.08 g,
at least about or less than about 0.1 g, at least about or less
than about 0.12 g, at least about or less than about 0.14 g, at
least about or less than about 0.16 g, at least about or less than
about 0.18 g, at least about or less than about 0.2 g, at least
about or less than about 0.22 g, at least about or less than about
0.24 g, at least about or less than about 0.26 g, at least about or
less than about 0.28 g, at least about or less than about 0.3 g, at
least about or less than about 0.32 g, at least about or less than
about 0.34 g, at least about or less than about 0.36 g, at least
about or less than about 0.38 g, at least about or less than about
0.4 g, at least about or less than about 0.42 g, at least about or
less than about 0.44 g, at least about or less than about 0.46 g,
at least about or less than about 0.48 g, at least about or less
than about 0.5 g, at least about or less than about 0.52 g, at
least about or less than about 0.54 g, at least about or less than
about 0.56 g, at least about or less than about 0.58 g, or at least
about or less than about 0.6 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 90 mg of at least one proton pump
inhibitor and at least about or less than about 0.02 g, at least
about or less than about 0.04 g, at least about or less than about
0.06 g, at least about or less than about 0.08 g, at least about or
less than about 0.1 g, at least about or less than about 0.12 g, at
least about or less than about 0.14 g, at least about or less than
about 0.16 g, at least about or less than about 0.18 g, at least
about or less than about 0.2 g, at least about or less than about
0.22 g, at least about or less than about 0.24 g, at least about or
less than about 0.26 g, at least about or less than about 0.28 g,
at least about or less than about 0.3 g, at least about or less
than about 0.32 g, at least about or less than about 0.34 g, at
least about or less than about 0.36 g, at least about or less than
about 0.38 g, at least about or less than about 0.4 g, at least
about or less than about 0.42 g, at least about or less than about
0.44 g, at least about or less than about 0.46 g, at least about or
less than about 0.48 g, at least about or less than about 0.5 g, at
least about or less than about 0.52 g, at least about or less than
about 0.54 g, at least about or less than about 0.56 g, at least
about or less than about 0.58 g, or at least about or less than
about 0.6 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 95 mg of at least one proton pump inhibitor and at least
about or less than about 0.02 g, at least about or less than about
0.04 g, at least about or less than about 0.06 g, at least about or
less than about 0.08 g, at least about or less than about 0.1 g, at
least about or less than about 0.12 g, at least about or less than
about 0.14 g, at least about or less than about 0.16 g, at least
about or less than about 0.18 g, at least about or less than about
0.2 g, at least about or less than about 0.22 g, at least about or
less than about 0.24 g, at least about or less than about 0.26 g,
at least about or less than about 0.28 g, at least about or less
than about 0.3 g, at least about or less than about 0.32 g, at
least about or less than about 0.34 g, at least about or less than
about 0.36 g, at least about or less than about 0.38 g, at least
about or less than about 0.4 g, at least about or less than about
0.42 g, at least about or less than about 0.44 g, at least about or
less than about 0.46 g, at least about or less than about 0.48 g,
at least about or less than about 0.5 g, at least about or less
than about 0.52 g, at least about or less than about 0.54 g, at
least about or less than about 0.56 g, at least about or less than
about 0.58 g, or at least about or less than about 0.6 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 100 mg of at least
one proton pump inhibitor and at least about or less than about
0.02 g, at least about or less than about 0.04 g, at least about or
less than about 0.06 g, at least about or less than about 0.08 g,
at least about or less than about 0.1 g, at least about or less
than about 0.12 g, at least about or less than about 0.14 g, at
least about or less than about 0.16 g, at least about or less than
about 0.18 g, at least about or less than about 0.2 g, at least
about or less than about 0.22 g, at least about or less than about
0.24 g, at least about or less than about 0.26 g, at least about or
less than about 0.28 g, at least about or less than about 0.3 g, at
least about or less than about 0.32 g, at least about or less than
about 0.34 g, at least about or less than about 0.36 g, at least
about or less than about 0.38 g, at least about or less than about
0.4 g, at least about or less than about 0.42 g, at least about or
less than about 0.44 g, at least about or less than about 0.46 g,
at least about or less than about 0.48 g, at least about or less
than about 0.5 g, at least about or less than about 0.52 g, at
least about or less than about 0.54 g, at least about or less than
about 0.56 g, at least about or less than about 0.58 g, or at least
about or less than about 0.6 g of at least one bile acid
sequestrant. In certain embodiments the at least one proton pump
inhibitor is omeprazole. In certain embodiments the at least one
proton pump inhibitor is esomeprazole. In certain embodiments the
at least one proton pump inhibitor is lansoprazole. In certain
embodiments the at least one proton pump inhibitor is pantoprazole.
In certain embodiments the at least one proton pump inhibitor is
rabeprazole. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole. In certain embodiments the at least one
bile acid sequestrant is cholestyramine. In certain embodiments the
at least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one bile acid sequestrant is
colesevelam-HCl. In certain embodiments the at least one bile acid
sequestrant is colestipol. In certain embodiments the at least one
proton pump inhibitor is omeprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is omeprazole and the at least one bile
acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is omeprazole and the at least one
bile acid sequestrant is colesevelam-HCl. In certain embodiments
the at least one proton pump inhibitor is omeprazole and the at
least one bile acid sequestrant is colestipol. In certain
embodiments the at least one proton pump inhibitor is esomeprazole
and the at least one bile acid sequestrant is cholestyramine. In
certain embodiments the at least one proton pump inhibitor is
esomeprazole and the at least one bile acid sequestrant is
colesevelam. In certain embodiments the at least one proton pump
inhibitor is esomeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is esomeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is lansoprazole and the at least one bile
acid sequestrant is cholestyramine. In certain embodiments the at
least one proton pump inhibitor is lansoprazole and the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one proton pump inhibitor is lansoprazole and the at
least one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is lansoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the at least one proton pump inhibitor is
pantoprazole and the at least one bile acid sequestrant is
cholestyramine. In certain embodiments the at least one proton pump
inhibitor is pantoprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is pantoprazole and the at least one bile
acid sequestrant is colesevelam-HCl. In certain embodiments the at
least one proton pump inhibitor is pantoprazole and the at least
one bile acid sequestrant is colestipol. In certain embodiments the
at least one proton pump inhibitor is rabeprazole and the at least
one bile acid sequestrant is cholestyramine. In certain embodiments
the at least one proton pump inhibitor is rabeprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is rabeprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
rabeprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is tenatoprazole and the at least one
bile acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is tenatoprazole and the at least
one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is tenatoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the dosage unit and daily dose are equivalent.
In various embodiments, the dosage unit is administered with food
at anytime of the day, without food at anytime of the day, with
food after an overnight fast (e.g. with breakfast), at bedtime
after a low fat snack. In various embodiments, the dosage unit is
administered once a day, twice a day, three times a day, four times
a day. The dosage unit can optionally comprise other agents such as
at least one antacid, at least one histamine Hz-receptor
antagonist, or combinations thereof.
In certain embodiments, the dosage unit comprises at least about or
less than about 5 mg of at least one proton pump inhibitor and at
least about or less than about 0.01 g, at least about or less than
about 0.02 g, at least about or less than about 0.03 g, at least
about or less than about 0.04 g, at least about or less than about
0.05 g, at least about or less than about 0.06 g, at least about or
less than about 0.07 g, at least about or less than about 0.08 g,
at least about or less than about 0.09 g, at least about or less
than about 0.1 g, at least about or less than about 0.11 g, at
least about or less than about 0.12 g, at least about or less than
about 0.13 g, at least about or less than about 0.14 g, at least
about or less than about 0.15 g, at least about or less than about
0.16 g, at least about or less than about 0.17 g, at least about or
less than about 0.18 g, at least about or less than about 0.19 g,
at least about or less than about 0.2 g, at least about or less
than about 0.21 g, at least about or less than about 0.22 g, at
least about or less than about 0.23 g, at least about or less than
about 0.24 g, at least about or less than about 0.25 g, at least
about or less than about 0.26 g, at least about or less than about
0.27 g, at least about or less than about 0.28 g, at least about or
less than about 0.29 g, or at least about or less than about 0.3 g
of at least one bile acid sequestrant. In certain embodiments, the
dosage unit comprises at least about or less than about 10 mg of at
least one proton pump inhibitor and at least about or less than
about 0.01 g, at least about or less than about 0.02 g, at least
about or less than about 0.03 g, at least about or less than about
0.04 g, at least about or less than about 0.05 g, at least about or
less than about 0.06 g, at least about or less than about 0.07 g,
at least about or less than about 0.08 g, at least about or less
than about 0.09 g, at least about or less than about 0.1 g, at
least about or less than about 0.11 g, at least about or less than
about 0.12 g, at least about or less than about 0.13 g, at least
about or less than about 0.14 g, at least about or less than about
0.15 g, at least about or less than about 0.16 g, at least about or
less than about 0.17 g, at least about or less than about 0.18 g,
at least about or less than about 0.19 g, at least about or less
than about 0.2 g, at least about or less than about 0.21 g, at
least about or less than about 0.22 g, at least about or less than
about 0.23 g, at least about or less than about 0.24 g, at least
about or less than about 0.25 g, at least about or less than about
0.26 g, at least about or less than about 0.27 g, at least about or
less than about 0.28 g, at least about or less than about 0.29 g,
or at least about or less than about 0.3 g of at least one bile
acid sequestrant. In certain embodiments, the dosage unit comprises
at least about or less than about 15 mg of at least one proton pump
inhibitor and at least about or less than about 0.01 g, at least
about or less than about 0.02 g, at least about or less than about
0.03 g, at least about or less than about 0.04 g, at least about or
less than about 0.05 g, at least about or less than about 0.06 g,
at least about or less than about 0.07 g, at least about or less
than about 0.08 g, at least about or less than about 0.09 g, at
least about or less than about 0.1 g, at least about or less than
about 0.11 g, at least about or less than about 0.12 g, at least
about or less than about 0.13 g, at least about or less than about
0.14 g, at least about or less than about 0.15 g, at least about or
less than about 0.16 g, at least about or less than about 0.17 g,
at least about or less than about 0.18 g, at least about or less
than about 0.19 g, at least about or less than about 0.2 g, at
least about or less than about 0.21 g, at least about or less than
about 0.22 g, at least about or less than about 0.23 g, at least
about or less than about 0.24 g, at least about or less than about
0.25 g, at least about or less than about 0.26 g, at least about or
less than about 0.27 g, at least about or less than about 0.28 g,
at least about or less than about 0.29 g, or at least about or less
than about 0.3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 20 mg of at least one proton pump inhibitor and at least
about or less than about 0.01 g, at least about or less than about
0.02 g, at least about or less than about 0.03 g, at least about or
less than about 0.04 g, at least about or less than about 0.05 g,
at least about or less than about 0.06 g, at least about or less
than about 0.07 g, at least about or less than about 0.08 g, at
least about or less than about 0.09 g, at least about or less than
about 0.1 g, at least about or less than about 0.11 g, at least
about or less than about 0.12 g, at least about or less than about
0.13 g, at least about or less than about 0.14 g, at least about or
less than about 0.15 g, at least about or less than about 0.16 g,
at least about or less than about 0.17 g, at least about or less
than about 0.18 g, at least about or less than about 0.19 g, at
least about or less than about 0.2 g, at least about or less than
about 0.21 g, at least about or less than about 0.22 g, at least
about or less than about 0.23 g, at least about or less than about
0.24 g, at least about or less than about 0.25 g, at least about or
less than about 0.26 g, at least about or less than about 0.27 g,
at least about or less than about 0.28 g, at least about or less
than about 0.29 g, or at least about or less than about 0.3 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 25 mg of at least
one proton pump inhibitor and at least about or less than about
0.01 g, at least about or less than about 0.02 g, at least about or
less than about 0.03 g, at least about or less than about 0.04 g,
at least about or less than about 0.05 g, at least about or less
than about 0.06 g, at least about or less than about 0.07 g, at
least about or less than about 0.08 g, at least about or less than
about 0.09 g, at least about or less than about 0.1 g, at least
about or less than about 0.11 g, at least about or less than about
0.12 g, at least about or less than about 0.13 g, at least about or
less than about 0.14 g, at least about or less than about 0.15 g,
at least about or less than about 0.16 g, at least about or less
than about 0.17 g, at least about or less than about 0.18 g, at
least about or less than about 0.19 g, at least about or less than
about 0.2 g, at least about or less than about 0.21 g, at least
about or less than about 0.22 g, at least about or less than about
0.23 g, at least about or less than about 0.24 g, at least about or
less than about 0.25 g, at least about or less than about 0.26 g,
at least about or less than about 0.27 g, at least about or less
than about 0.28 g, at least about or less than about 0.29 g, or at
least about or less than about 0.3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 30 mg of at least one proton pump
inhibitor and at least about or less than about 0.01 g, at least
about or less than about 0.02 g, at least about or less than about
0.03 g, at least about or less than about 0.04 g, at least about or
less than about 0.05 g, at least about or less than about 0.06 g,
at least about or less than about 0.07 g, at least about or less
than about 0.08 g, at least about or less than about 0.09 g, at
least about or less than about 0.1 g, at least about or less than
about 0.11 g, at least about or less than about 0.12 g, at least
about or less than about 0.13 g, at least about or less than about
0.14 g, at least about or less than about 0.15 g, at least about or
less than about 0.16 g, at least about or less than about 0.17 g,
at least about or less than about 0.18 g, at least about or less
than about 0.19 g, at least about or less than about 0.2 g, at
least about or less than about 0.21 g, at least about or less than
about 0.22 g, at least about or less than about 0.23 g, at least
about or less than about 0.24 g, at least about or less than about
0.25 g, at least about or less than about 0.26 g, at least about or
less than about 0.27 g, at least about or less than about 0.28 g,
at least about or less than about 0.29 g, or at least about or less
than about 0.3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 35 mg of at least one proton pump inhibitor and at least
about or less than about 0.01 g, at least about or less than about
0.02 g, at least about or less than about 0.03 g, at least about or
less than about 0.04 g, at least about or less than about 0.05 g,
at least about or less than about 0.06 g, at least about or less
than about 0.07 g, at least about or less than about 0.08 g, at
least about or less than about 0.09 g, at least about or less than
about 0.1 g, at least about or less than about 0.11 g, at least
about or less than about 0.12 g, at least about or less than about
0.13 g, at least about or less than about 0.14 g, at least about or
less than about 0.15 g, at least about or less than about 0.16 g,
at least about or less than about 0.17 g, at least about or less
than about 0.18 g, at least about or less than about 0.19 g, at
least about or less than about 0.2 g, at least about or less than
about 0.21 g, at least about or less than about 0.22 g, at least
about or less than about 0.23 g, at least about or less than about
0.24 g, at least about or less than about 0.25 g, at least about or
less than about 0.26 g, at least about or less than about 0.27 g,
at least about or less than about 0.28 g, at least about or less
than about 0.29 g, or at least about or less than about 0.3 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 40 mg of at least
one proton pump inhibitor and at least about or less than about
0.01 g, at least about or less than about 0.02 g, at least about or
less than about 0.03 g, at least about or less than about 0.04 g,
at least about or less than about 0.05 g, at least about or less
than about 0.06 g, at least about or less than about 0.07 g, at
least about or less than about 0.08 g, at least about or less than
about 0.09 g, at least about or less than about 0.1 g, at least
about or less than about 0.11 g, at least about or less than about
0.12 g, at least about or less than about 0.13 g, at least about or
less than about 0.14 g, at least about or less than about 0.15 g,
at least about or less than about 0.16 g, at least about or less
than about 0.17 g, at least about or less than about 0.18 g, at
least about or less than about 0.19 g, at least about or less than
about 0.2 g, at least about or less than about 0.21 g, at least
about or less than about 0.22 g, at least about or less than about
0.23 g, at least about or less than about 0.24 g, at least about or
less than about 0.25 g, at least about or less than about 0.26 g,
at least about or less than about 0.27 g, at least about or less
than about 0.28 g, at least about or less than about 0.29 g, or at
least about or less than about 0.3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 45 mg of at least one proton pump
inhibitor and at least about or less than about 0.01 g, at least
about or less than about 0.02 g, at least about or less than about
0.03 g, at least about or less than about 0.04 g, at least about or
less than about 0.05 g, at least about or less than about 0.06 g,
at least about or less than about 0.07 g, at least about or less
than about 0.08 g, at least about or less than about 0.09 g, at
least about or less than about 0.1 g, at least about or less than
about 0.11 g, at least about or less than about 0.12 g, at least
about or less than about 0.13 g, at least about or less than about
0.14 g, at least about or less than about 0.15 g, at least about or
less than about 0.16 g, at least about or less than about 0.17 g,
at least about or less than about 0.18 g, at least about or less
than about 0.19 g, at least about or less than about 0.2 g, at
least about or less than about 0.21 g, at least about or less than
about 0.22 g, at least about or less than about 0.23 g, at least
about or less than about 0.24 g, at least about or less than about
0.25 g, at least about or less than about 0.26 g, at least about or
less than about 0.27 g, at least about or less than about 0.28 g,
at least about or less than about 0.29 g, or at least about or less
than about 0.3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 50 mg of at least one proton pump inhibitor and at least
about or less than about 0.01 g, at least about or less than about
0.02 g, at least about or less than about 0.03 g, at least about or
less than about 0.04 g, at least about or less than about 0.05 g,
at least about or less than about 0.06 g, at least about or less
than about 0.07 g, at least about or less than about 0.08 g, at
least about or less than about 0.09 g, at least about or less than
about 0.1 g, at least about or less than about 0.11 g, at least
about or less than about 0.12 g, at least about or less than about
0.13 g, at least about or less than about 0.14 g, at least about or
less than about 0.15 g, at least about or less than about 0.16 g,
at least about or less than about 0.17 g, at least about or less
than about 0.18 g, at least about or less than about 0.19 g, at
least about or less than about 0.2 g, at least about or less than
about 0.21 g, at least about or less than about 0.22 g, at least
about or less than about 0.23 g, at least about or less than about
0.24 g, at least about or less than about 0.25 g, at least about or
less than about 0.26 g, at least about or less than about 0.27 g,
at least about or less than about 0.28 g, at least about or less
than about 0.29 g, or at least about or less than about 0.3 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 55 mg of at least
one proton pump inhibitor and at least about or less than about
0.01 g, at least about or less than about 0.02 g, at least about or
less than about 0.03 g, at least about or less than about 0.04 g,
at least about or less than about 0.05 g, at least about or less
than about 0.06 g, at least about or less than about 0.07 g, at
least about or less than about 0.08 g, at least about or less than
about 0.09 g, at least about or less than about 0.1 g, at least
about or less than about 0.11 g, at least about or less than about
0.12 g, at least about or less than about 0.13 g, at least about or
less than about 0.14 g, at least about or less than about 0.15 g,
at least about or less than about 0.16 g, at least about or less
than about 0.17 g, at least about or less than about 0.18 g, at
least about or less than about 0.19 g, at least about or less than
about 0.2 g, at least about or less than about 0.21 g, at least
about or less than about 0.22 g, at least about or less than about
0.23 g, at least about or less than about 0.24 g, at least about or
less than about 0.25 g, at least about or less than about 0.26 g,
at least about or less than about 0.27 g, at least about or less
than about 0.28 g, at least about or less than about 0.29 g, or at
least about or less than about 0.3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 60 mg of at least one proton pump
inhibitor and at least about or less than about 0.01 g, at least
about or less than about 0.02 g, at least about or less than about
0.03 g, at least about or less than about 0.04 g, at least about or
less than about 0.05 g, at least about or less than about 0.06 g,
at least about or less than about 0.07 g, at least about or less
than about 0.08 g, at least about or less than about 0.09 g, at
least about or less than about 0.1 g, at least about or less than
about 0.11 g, at least about or less than about 0.12 g, at least
about or less than about 0.13 g, at least about or less than about
0.14 g, at least about or less than about 0.15 g, at least about or
less than about 0.16 g, at least about or less than about 0.17 g,
at least about or less than about 0.18 g, at least about or less
than about 0.19 g, at least about or less than about 0.2 g, at
least about or less than about 0.21 g, at least about or less than
about 0.22 g, at least about or less than about 0.23 g, at least
about or less than about 0.24 g, at least about or less than about
0.25 g, at least about or less than about 0.26 g, at least about or
less than about 0.27 g, at least about or less than about 0.28 g,
at least about or less than about 0.29 g, or at least about or less
than about 0.3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 65 mg of at least one proton pump inhibitor and at least
about or less than about 0.01 g, at least about or less than about
0.02 g, at least about or less than about 0.03 g, at least about or
less than about 0.04 g, at least about or less than about 0.05 g,
at least about or less than about 0.06 g, at least about or less
than about 0.07 g, at least about or less than about 0.08 g, at
least about or less than about 0.09 g, at least about or less than
about 0.1 g, at least about or less than about 0.11 g, at least
about or less than about 0.12 g, at least about or less than about
0.13 g, at least about or less than about 0.14 g, at least about or
less than about 0.15 g, at least about or less than about 0.16
g, at least about or less than about 0.17 g, at least about or less
than about 0.18 g, at least about or less than about 0.19 g, at
least about or less than about 0.2 g, at least about or less than
about 0.21 g, at least about or less than about 0.22 g, at least
about or less than about 0.23 g, at least about or less than about
0.24 g, at least about or less than about 0.25 g, at least about or
less than about 0.26 g, at least about or less than about 0.27 g,
at least about or less than about 0.28 g, at least about or less
than about 0.29 g, or at least about or less than about 0.3 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 70 mg of at least
one proton pump inhibitor and at least about or less than about
0.01 g, at least about or less than about 0.02 g, at least about or
less than about 0.03 g, at least about or less than about 0.04 g,
at least about or less than about 0.05 g, at least about or less
than about 0.06 g, at least about or less than about 0.07 g, at
least about or less than about 0.08 g, at least about or less than
about 0.09 g, at least about or less than about 0.1 g, at least
about or less than about 0.11 g, at least about or less than about
0.12 g, at least about or less than about 0.13 g, at least about or
less than about 0.14 g, at least about or less than about 0.15 g,
at least about or less than about 0.16 g, at least about or less
than about 0.17 g, at least about or less than about 0.18 g, at
least about or less than about 0.19 g, at least about or less than
about 0.2 g, at least about or less than about 0.21 g, at least
about or less than about 0.22 g, at least about or less than about
0.23 g, at least about or less than about 0.24 g, at least about or
less than about 0.25 g, at least about or less than about 0.26 g,
at least about or less than about 0.27 g, at least about or less
than about 0.28 g, at least about or less than about 0.29 g, or at
least about or less than about 0.3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 75 mg of at least one proton pump
inhibitor and at least about or less than about 0.01 g, at least
about or less than about 0.02 g, at least about or less than about
0.03 g, at least about or less than about 0.04 g, at least about or
less than about 0.05 g, at least about or less than about 0.06 g,
at least about or less than about 0.07 g, at least about or less
than about 0.08 g, at least about or less than about 0.09 g, at
least about or less than about 0.1 g, at least about or less than
about 0.11 g, at least about or less than about 0.12 g, at least
about or less than about 0.13 g, at least about or less than about
0.14 g, at least about or less than about 0.15 g, at least about or
less than about 0.16 g, at least about or less than about 0.17 g,
at least about or less than about 0.18 g, at least about or less
than about 0.19 g, at least about or less than about 0.2 g, at
least about or less than about 0.21 g, at least about or less than
about 0.22 g, at least about or less than about 0.23 g, at least
about or less than about 0.24 g, at least about or less than about
0.25 g, at least about or less than about 0.26 g, at least about or
less than about 0.27 g, at least about or less than about 0.28 g,
at least about or less than about 0.29 g, or at least about or less
than about 0.3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 80 mg of at least one proton pump inhibitor and at least
about or less than about 0.01 g, at least about or less than about
0.02 g, at least about or less than about 0.03 g, at least about or
less than about 0.04 g, at least about or less than about 0.05 g,
at least about or less than about 0.06 g, at least about or less
than about 0.07 g, at least about or less than about 0.08 g, at
least about or less than about 0.09 g, at least about or less than
about 0.1 g, at least about or less than about 0.11 g, at least
about or less than about 0.12 g, at least about or less than about
0.13 g, at least about or less than about 0.14 g, at least about or
less than about 0.15 g, at least about or less than about 0.16 g,
at least about or less than about 0.17 g, at least about or less
than about 0.18 g, at least about or less than about 0.19 g, at
least about or less than about 0.2 g, at least about or less than
about 0.21 g, at least about or less than about 0.22 g, at least
about or less than about 0.23 g, at least about or less than about
0.24 g, at least about or less than about 0.25 g, at least about or
less than about 0.26 g, at least about or less than about 0.27 g,
at least about or less than about 0.28 g, at least about or less
than about 0.29 g, or at least about or less than about 0.3 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 85 mg of at least
one proton pump inhibitor and at least about or less than about
0.01 g, at least about or less than about 0.02 g, at least about or
less than about 0.03 g, at least about or less than about 0.04 g,
at least about or less than about 0.05 g, at least about or less
than about 0.06 g, at least about or less than about 0.07 g, at
least about or less than about 0.08 g, at least about or less than
about 0.09 g, at least about or less than about 0.1 g, at least
about or less than about 0.11 g, at least about or less than about
0.12 g, at least about or less than about 0.13 g, at least about or
less than about 0.14 g, at least about or less than about 0.15 g,
at least about or less than about 0.16 g, at least about or less
than about 0.17 g, at least about or less than about 0.18 g, at
least about or less than about 0.19 g, at least about or less than
about 0.2 g, at least about or less than about 0.21 g, at least
about or less than about 0.22 g, at least about or less than about
0.23 g, at least about or less than about 0.24 g, at least about or
less than about 0.25 g, at least about or less than about 0.26 g,
at least about or less than about 0.27 g, at least about or less
than about 0.28 g, at least about or less than about 0.29 g, or at
least about or less than about 0.3 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 90 mg of at least one proton pump
inhibitor and at least about or less than about 0.01 g, at least
about or less than about 0.02 g, at least about or less than about
0.03 g, at least about or less than about 0.04 g, at least about or
less than about 0.05 g, at least about or less than about 0.06 g,
at least about or less than about 0.07 g, at least about or less
than about 0.08 g, at least about or less than about 0.09 g, at
least about or less than about 0.1 g, at least about or less than
about 0.11 g, at least about or less than about 0.12 g, at least
about or less than about 0.13 g, at least about or less than about
0.14 g, at least about or less than about 0.15 g, at least about or
less than about 0.16 g, at least about or less than about 0.17 g,
at least about or less than about 0.18 g, at least about or less
than about 0.19 g, at least about or less than about 0.2 g, at
least about or less than about 0.21 g, at least about or less than
about 0.22 g, at least about or less than about 0.23 g, at least
about or less than about 0.24 g, at least about or less than about
0.25 g, at least about or less than about 0.26 g, at least about or
less than about 0.27 g, at least about or less than about 0.28 g,
at least about or less than about 0.29 g, or at least about or less
than about 0.3 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 95 mg of at least one proton pump inhibitor and at least
about or less than about 0.01 g, at least about or less than about
0.02 g, at least about or less than about 0.03 g, at least about or
less than about 0.04 g, at least about or less than about 0.05 g,
at least about or less than about 0.06 g, at least about or less
than about 0.07 g, at least about or less than about 0.08 g, at
least about or less than about 0.09 g, at least about or less than
about 0.1 g, at least about or less than about 0.11 g, at least
about or less than about 0.12 g, at least about or less than about
0.13 g, at least about or less than about 0.14 g, at least about or
less than about 0.15 g, at least about or less than about 0.16 g,
at least about or less than about 0.17 g, at least about or less
than about 0.18 g, at least about or less than about 0.19 g, at
least about or less than about 0.2 g, at least about or less than
about 0.21 g, at least about or less than about 0.22 g, at least
about or less than about 0.23 g, at least about or less than about
0.24 g, at least about or less than about 0.25 g, at least about or
less than about 0.26 g, at least about or less than about 0.27 g,
at least about or less than about 0.28 g, at least about or less
than about 0.29 g, or at least about or less than about 0.3 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 100 mg of at least
one proton pump inhibitor and at least about or less than about
0.01 g, at least about or less than about 0.02 g, at least about or
less than about 0.03 g, at least about or less than about 0.04 g,
at least about or less than about 0.05 g, at least about or less
than about 0.06 g, at least about or less than about 0.07 g, at
least about or less than about 0.08 g, at least about or less than
about 0.09 g, at least about or less than about 0.1 g, at least
about or less than about 0.11 g, at least about or less than about
0.12 g, at least about or less than about 0.13 g, at least about or
less than about 0.14 g, at least about or less than about 0.15 g,
at least about or less than about 0.16 g, at least about or less
than about 0.17 g, at least about or less than about 0.18 g, at
least about or less than about 0.19 g, at least about or less than
about 0.2 g, at least about or less than about 0.21 g, at least
about or less than about 0.22 g, at least about or less than about
0.23 g, at least about or less than about 0.24 g, at least about or
less than about 0.25 g, at least about or less than about 0.26 g,
at least about or less than about 0.27 g, at least about or less
than about 0.28 g, at least about or less than about 0.29 g, or at
least about or less than about 0.3 g of at least one bile acid
sequestrant. In certain embodiments the at least one proton pump
inhibitor is omeprazole. In certain embodiments the at least one
proton pump inhibitor is esomeprazole. In certain embodiments the
at least one proton pump inhibitor is lansoprazole. In certain
embodiments the at least one proton pump inhibitor is pantoprazole.
In certain embodiments the at least one proton pump inhibitor is
rabeprazole. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole. In certain embodiments the at least one
bile acid sequestrant is cholestyramine. In certain embodiments the
at least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one bile acid sequestrant is
colesevelam-HCl. In certain embodiments the at least one bile acid
sequestrant is colestipol. In certain embodiments the at least one
proton pump inhibitor is omeprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is omeprazole and the at least one bile
acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is omeprazole and the at least one
bile acid sequestrant is colesevelam-HCl. In certain embodiments
the at least one proton pump inhibitor is omeprazole and the at
least one bile acid sequestrant is colestipol. In certain
embodiments the at least one proton pump inhibitor is esomeprazole
and the at least one bile acid sequestrant is cholestyramine. In
certain embodiments the at least one proton pump inhibitor is
esomeprazole and the at least one bile acid sequestrant is
colesevelam. In certain embodiments the at least one proton pump
inhibitor is esomeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is esomeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is lansoprazole and the at least one bile
acid sequestrant is cholestyramine. In certain embodiments the at
least one proton pump inhibitor is lansoprazole and the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one proton pump inhibitor is lansoprazole and the at
least one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is lansoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the at least one proton pump inhibitor is
pantoprazole and the at least one bile acid sequestrant is
cholestyramine. In certain embodiments the at least one proton pump
inhibitor is pantoprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is pantoprazole and the at least one bile
acid sequestrant is colesevelam-HCl. In certain embodiments the at
least one proton pump inhibitor is pantoprazole and the at least
one bile acid sequestrant is colestipol. In certain embodiments the
at least one proton pump inhibitor is rabeprazole and the at least
one bile acid sequestrant is cholestyramine. In certain embodiments
the at least one proton pump inhibitor is rabeprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is rabeprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
rabeprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is tenatoprazole and the at least one
bile acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is tenatoprazole and the at least
one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is tenatoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the dosage unit and daily dose are equivalent.
In various embodiments, the dosage unit is administered with food
at anytime of the day, without food at anytime of the day, with
food after an overnight fast (e.g. with breakfast), at bedtime
after a low fat snack. In various embodiments, the dosage unit is
administered once a day, twice a day, three times a day, four times
a day. The dosage unit can optionally comprise other agents such as
at least one antacid, at least one histamine Hz-receptor
antagonist, or combinations thereof.
In certain embodiments, the dosage unit comprises at least about or
less than about 5 mg of at least one proton pump inhibitor and at
least about or less than about 5 g, at least about or less than
about 10 g, at least about or less than about 15 g, at least about
or less than about 20 g, at least about or less than about 25 g, at
least about or less than about 30 g, at least about or less than
about 35 g, at least about or less than about 40 g, at least about
or less than about 45 g, at least about or less than about 50 g, at
least about or less than about 55 g, at least about or less than
about 60 g, at least about or less than about 65 g, at least about
or less than about 70 g, at least about or less than about 75 g, at
least about or less than about 80 g, at least about or less than
about 85 g, at least about or less than about 90 g, at least about
or less than about 95 g, at least about or less than about 100 g,
at least about or less than about 105 g, at least about or less
than about 110 g, at least about or less than about 115 g, at least
about or less than about 120 g, at least about or less than about
125 g, at least about or less than about 130 g, at least about or
less than about 135 g, at least about or less than about 140 g, at
least about or less than about 145 g, or at least about or less
than about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 10 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 15 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 20 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 25 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 30 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 35 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 40 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 45 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 50 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 55 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 60 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 65 mg of at least one proton pump inhibitor and at least
about or less than about 5 g, at least about or less than about 10
g, at least about or less than about 15 g, at least about or less
than about 20 g, at least about or less than about 25 g, at least
about or less than about 30 g, at least about or less than about 35
g, at least about or less than about 40 g, at least about or less
than about 45 g, at least about or less than about 50 g, at least
about or less than about 55 g, at least about or less than about 60
g, at least about or less than about 65 g, at least about or less
than about 70 g, at least about or less than about 75 g, at least
about or less than about 80 g, at least about or less than about 85
g, at least about or less than about 90 g, at least about or less
than about 95 g, at least about or less than about 100 g, at least
about or less than about 105 g, at least about or less than about
110 g, at least about or less than about 115 g, at least about or
less than about 120 g, at least about or less than about 125 g, at
least about or less than about 130 g, at least about or less than
about 135 g, at least about or less than about 140 g, at least
about or less than about 145 g, or at least about or less than
about 150 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least
about or less than about 70 mg of at least one proton pump
inhibitor and at least about or less than about 5 g, at least about
or less than about 10 g, at least about or less than about 15 g, at
least about or less than about 20 g, at least about or less than
about 25 g, at least about or less than about 30 g, at least about
or less than about 35 g, at least about or less than about 40 g, at
least about or less than about 45 g, at least about or less than
about 50 g, at least about or less than about 55 g, at least about
or less than about 60 g, at least about or less than about 65 g, at
least about or less than about 70 g, at least about or less than
about 75 g, at least about or less than about 80 g, at least about
or less than about 85 g, at least about or less than about 90 g, at
least about or less than about 95 g, at least about or less than
about 100 g, at least about or less than about 105 g, at least
about or less than about 110 g, at least about or less than about
115 g, at least about or less than about 120 g, at least about or
less than about 125 g, at least about or less than about 130 g, at
least about or less than about 135 g, at least about or less than
about 140 g, at least about or less than about 145 g, or at least
about or less than about 150 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 75 mg of at least one proton pump
inhibitor and at least about or less than about 5 g, at least about
or less than about 10 g, at least about or less than about 15 g, at
least about or less than about 20 g, at least about or less than
about 25 g, at least about or less than about 30 g, at least about
or less than about 35 g, at least about or less than about 40 g, at
least about or less than about 45 g, at least about or less than
about 50 g, at least about or less than about 55 g, at least about
or less than about 60 g, at least about or less than about 65 g, at
least about or less than about 70 g, at least about or less than
about 75 g, at least about or less than about 80 g, at least about
or less than about 85 g, at least about or less than about 90 g, at
least about or less than about 95 g, at least about or less than
about 100 g, at least about or less than about 105 g, at least
about or less than about 110 g, at least about or less than about
115 g, at least about or less than about 120 g, at least about or
less than about 125 g, at least about or less than about 130 g, at
least about or less than about 135 g, at least about or less than
about 140 g, at least about or less than about 145 g, or at least
about or less than about 150 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 80 mg of at least one proton pump
inhibitor and at least about or less than about 5 g, at least about
or less than about 10 g, at least about or less than about 15 g, at
least about or less than about 20 g, at least about or less than
about 25 g, at least about or less than about 30 g, at least about
or less than about 35 g, at least about or less than about 40 g, at
least about or less than about 45 g, at least about or less than
about 50 g, at least about or less than about 55 g, at least about
or less than about 60 g, at least about or less than about 65 g, at
least about or less than about 70 g, at least about or less than
about 75 g, at least about or less than about 80 g, at least about
or less than about 85 g, at least about or less than about 90 g, at
least about or less than about 95 g, at least about or less than
about 100 g, at least about or less than about 105 g, at least
about or less than about 110 g, at least about or less than about
115 g, at least about or less than about 120 g, at least about or
less than about 125 g, at least about or less than about 130 g, at
least about or less than about 135 g, at least about or less than
about 140 g, at least about or less than about 145 g, or at least
about or less than about 150 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 85 mg of at least one proton pump
inhibitor and at least about or less than about 5 g, at least about
or less than about 10 g, at least about or less than about 15 g, at
least about or less than about 20 g, at least about or less than
about 25 g, at least about or less than about 30 g, at least about
or less than about 35 g, at least about or less than about 40 g, at
least about or less than about 45 g, at least about or less than
about 50 g, at least about or less than about 55 g, at least about
or less than about 60 g, at least about or less than about 65 g, at
least about or less than about 70 g, at least about or less than
about 75 g, at least about or less than about 80 g, at least about
or less than about 85 g, at least about or less than about 90 g, at
least about or less than about 95 g, at least about or less than
about 100 g, at least about or less than about 105 g, at least
about or less than about 110 g, at least about or less than about
115 g, at least about or less than about 120 g, at least about or
less than about 125 g, at least about or less than about 130 g, at
least about or less than about 135 g, at least about or less than
about 140 g, at least about or less than about 145 g, or at least
about or less than about 150 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 90 mg of at least one proton pump
inhibitor and at least about or less than about 5 g, at least about
or less than about 10 g, at least about or less than about 15 g, at
least about or less than about 20 g, at least about or less than
about 25 g, at least about or less than about 30 g, at least about
or less than about 35 g, at least about or less than about 40 g, at
least about or less than about 45 g, at least about or less than
about 50 g, at least about or less than about 55 g, at least about
or less than about 60 g, at least about or less than about 65 g, at
least about or less than about 70 g, at least about or less than
about 75 g, at least about or less than about 80 g, at least about
or less than about 85 g, at least about or less than about 90 g, at
least about or less than about 95 g, at least about or less than
about 100 g, at least about or less than about 105 g, at least
about or less than about 110 g, at least about or less than about
115 g, at least about or less than about 120 g, at least about or
less than about 125 g, at least about or less than about 130 g, at
least about or less than about 135 g, at least about or less than
about 140 g, at least about or less than about 145 g, or at least
about or less than about 150 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 95 mg of at least one proton pump
inhibitor and at least about or less than about 5 g, at least about
or less than about 10 g, at least about or less than about 15 g, at
least about or less than about 20 g, at least about or less than
about 25 g, at least about or less than about 30 g, at least about
or less than about 35 g, at least about or less than about 40 g, at
least about or less than about 45 g, at least about or less than
about 50 g, at least about or less than about 55 g, at least about
or less than about 60 g, at least about or less than about 65 g, at
least about or less than about 70 g, at least about or less than
about 75 g, at least about or less than about 80 g, at least about
or less than about 85 g, at least about or less than about 90 g, at
least about or less than about 95 g, at least about or less than
about 100 g, at least about or less than about 105 g, at least
about or less than about 110 g, at least about or less than about
115 g, at least about or less than about 120 g, at least about or
less than about 125 g, at least about or less than about 130 g, at
least about or less than about 135 g, at least about or less than
about 140 g, at least about or less than about 145 g, or at least
about or less than about 150 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 100 mg of at least one proton pump
inhibitor and at least about or less than about 5 g, at least about
or less than about 10 g, at least about or less than about 15 g, at
least about or less than about 20 g, at least about or less than
about 25 g, at least about or less than about 30 g, at least about
or less than about 35 g, at least about or less than about 40 g, at
least about or less than about 45 g, at least about or less than
about 50 g, at least about or less than about 55 g, at least about
or less than about 60 g, at least about or less than about 65 g, at
least about or less than about 70 g, at least about or less than
about 75 g, at least about or less than about 80 g, at least about
or less than about 85 g, at least about or less than about 90 g, at
least about or less than about 95 g, at least about or less than
about 100 g, at least about or less than about 105 g, at least
about or less than about 110 g, at least about or less than about
115 g, at least about or less than about 120 g, at least about or
less than about 125 g, at least about or less than about 130 g, at
least about or less than about 135 g, at least about or less than
about 140 g, at least about or less than about 145 g, or at least
about or less than about 150 g of at least one bile acid
sequestrant. In certain embodiments the at least one proton pump
inhibitor is omeprazole. In certain embodiments the at least one
proton pump inhibitor is esomeprazole. In certain embodiments the
at least one proton pump inhibitor is lansoprazole. In certain
embodiments the at least one proton pump inhibitor is pantoprazole.
In certain embodiments the at least one proton pump inhibitor is
rabeprazole. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole. In certain embodiments the at least one
bile acid sequestrant is cholestyramine. In certain embodiments the
at least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one bile acid sequestrant is
colesevelam-HCl. In certain embodiments the at least one bile acid
sequestrant is colestipol. In certain embodiments the at least one
proton pump inhibitor is omeprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is omeprazole and the at least one bile
acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is omeprazole and the at least one
bile acid sequestrant is colesevelam-HCl. In certain embodiments
the at least one proton pump inhibitor is omeprazole and the at
least one bile acid sequestrant is colestipol. In certain
embodiments the at least one proton pump inhibitor is esomeprazole
and the at least one bile acid sequestrant is cholestyramine. In
certain embodiments the at least one proton pump inhibitor is
esomeprazole and the at least one bile acid sequestrant is
colesevelam. In certain embodiments the at least one proton pump
inhibitor is esomeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is esomeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is lansoprazole and the at least one bile
acid sequestrant is cholestyramine. In certain embodiments the at
least one proton pump inhibitor is lansoprazole and the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one proton pump inhibitor is lansoprazole and the at
least one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is lansoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the at least one proton pump inhibitor is
pantoprazole and the at least one bile acid sequestrant is
cholestyramine. In certain embodiments the at least one proton pump
inhibitor is pantoprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is pantoprazole and the at least one bile
acid sequestrant is colesevelam-HCl. In certain embodiments the at
least one proton pump inhibitor is pantoprazole and the at least
one bile acid sequestrant is colestipol. In certain embodiments the
at least one proton pump inhibitor is rabeprazole and the at least
one bile acid sequestrant is cholestyramine. In certain embodiments
the at least one proton pump inhibitor is rabeprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is rabeprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
rabeprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is tenatoprazole and the at least one
bile acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is tenatoprazole and the at least
one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is tenatoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the dosage unit and daily dose are equivalent.
In various embodiments, the dosage unit is administered with food
at anytime of the day, without food at anytime of the day, with
food after an overnight fast (e.g. with breakfast), at bedtime
after a low fat snack. In various embodiments, the dosage unit is
administered once a day, twice a day, three times a day, four times
a day. The dosage unit can optionally comprise other agents such as
at least one antacid, at least one histamine Hz-receptor
antagonist, or combinations thereof.
In certain embodiments, the dosage unit comprises at least about or
less than about 5 mg of at least one proton pump inhibitor and at
least about or less than about 2 g, at least about or less than
about 4 g, at least about or less than about 6 g, at least about or
less than about 8 g, at least about or less than about 10 g, at
least about or less than about 12 g, at least about or less than
about 14 g, at least about or less than about 16 g, at least about
or less than about 18 g, at least about or less than about 20 g, at
least about or less than about 22 g, at least about or less than
about 24 g, at least about or less than about 26 g, at least about
or less than about 28 g, at least about or less than about 30 g, at
least about or less than about 32 g, at least about or less than
about 34 g, at least about or less than about 36 g, at least about
or less than about 38 g, at least about or less than about 40 g, at
least about or less than about 42 g, at least about or less than
about 44 g, at least about or less than about 46 g, at least about
or less than about 48 g, at least about or less than about 50 g, at
least about or less than about 52 g, at least about or less than
about 54 g, at least about or less than about 56 g, at least about
or less than about 58 g, or at least about or less than about 60 g
of at least one bile acid sequestrant. In certain embodiments, the
dosage unit comprises at least about or less than about 10 mg of at
least one proton pump inhibitor and at least about or less than
about 2 g, at least about or less than about 4 g, at least about or
less than about 6 g, at least about or less than about 8 g, at
least about or less than about 10 g, at least about or less than
about 12 g, at least about or less than about 14 g, at least about
or less than about 16 g, at least about or less than about 18 g, at
least about or less than about 20 g, at least about or less than
about 22 g, at least about or less than about 24 g, at least about
or less than about 26 g, at least about or less than about 28 g, at
least about or less than about 30 g, at least about or less than
about 32 g, at least about or less than about 34 g, at least about
or less than about 36 g, at least about or less than about 38 g, at
least about or less than about 40 g, at least about or less than
about 42 g, at least about or less than about 44 g, at least about
or less than about 46 g, at least about or less than about 48 g, at
least about or less than about 50 g, at least about or less than
about 52 g, at least about or less than about 54 g, at least about
or less than about 56 g, at least about or less than about 58 g, or
at least about or less than about 60 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 15 mg of at least one proton pump
inhibitor and at least about or less than about 2 g, at least about
or less than about 4 g, at least about or less than about 6 g, at
least about or less than about 8 g, at least about or less than
about 10 g, at least about or less than about 12 g, at least about
or less than about 14 g, at least about or less than about 16 g, at
least about or less than about 18 g, at least about or less than
about 20 g, at least about or less than about 22 g, at least about
or less than about 24 g, at least about or less than about 26 g, at
least about or less than about 28 g, at least about or less than
about 30 g, at least about or less than about 32 g, at least about
or less than about 34 g, at least about or less than about 36 g, at
least about or less than about 38 g, at least about or less than
about 40 g, at least about or less than about 42 g, at least about
or less than about 44 g, at least about or less than about 46 g, at
least about or less than about 48 g, at least about or less than
about 50 g, at least about or less than about 52 g, at least about
or less than about 54 g, at least about or less than about 56 g, at
least about or less than about 58 g, or at least about or less than
about 60 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 20 mg of at least one proton pump inhibitor and at least
about or less than about 2 g, at least about or less than about 4
g, at least about or less than about 6 g, at least about or less
than about 8 g, at least about or less than about 10 g, at least
about or less than about 12 g, at least about or less than about 14
g, at least about or less than about 16 g, at least about or less
than about 18 g, at least about or less than about 20 g, at least
about or less than about 22 g, at least about or less than about 24
g, at least about or less than about 26 g, at least about or less
than about 28 g, at least about or less than about 30 g, at least
about or less than about 32 g, at least about or less than about 34
g, at least about or less than about 36 g, at least about or less
than about 38 g, at least about or less than about 40 g, at least
about or less than about 42 g, at least about or less than about 44
g, at least about or less than about 46 g, at least about or less
than about 48 g, at least about or less than about 50 g, at least
about or less than about 52 g, at least about or less than about 54
g, at least about or less than about 56 g, at least about or less
than about 58 g, or at least about or less than about 60 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 25 mg of at least
one proton pump inhibitor and at least about or less than about 2
g, at least about or less than about 4 g, at least about or less
than about 6 g, at least about or less than about 8 g, at least
about or less than about 10 g, at least about or less than about 12
g, at least about or less than about 14 g, at least about or less
than about 16 g, at least about or less than about 18 g, at least
about or less than about 20 g, at least about or less than about 22
g, at least about or less than about 24 g, at least about or less
than about 26 g, at least about or less than about 28 g, at least
about or less than about 30 g, at least about or less than about 32
g, at least about or less than about 34 g, at least about or less
than about 36 g, at least about or less than about 38 g, at least
about or less than about 40 g, at least about or less than about 42
g, at least about or less than about 44 g, at least about or less
than about 46 g, at least about or less than about 48 g, at least
about or less than about 50 g, at least about or less than about 52
g, at least about or less than about 54 g, at least about or less
than about 56 g, at least about or less than about 58 g, or at
least about or less than about 60 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 30 mg of at least one proton pump
inhibitor and at least about or less than about 2 g, at least about
or less than about 4 g, at least about or less than about 6 g, at
least about or less than about 8 g, at least about or less than
about 10 g, at least about or less than about 12 g, at least about
or less than about 14 g, at least about or less than about 16 g, at
least about or less than about 18 g, at least about or less than
about 20 g, at least about or less than about 22 g, at least about
or less than about 24 g, at least about or less than about 26 g, at
least about or less than about 28 g, at least about or less than
about 30 g, at least about or less than about 32 g, at least about
or less than about 34 g, at least about or less than about 36 g, at
least about or less than about 38 g, at least about or less than
about 40 g, at least about or less than about 42 g, at least about
or less than about 44 g, at least about or less than about 46 g, at
least about or less than about 48 g, at least about or less than
about 50 g, at least about or less than about 52 g, at least about
or less than about 54 g, at least about or less than about 56 g, at
least about or less than about 58 g, or at least about or less than
about 60 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 35 mg of at least one proton pump inhibitor and at least
about or less than about 2 g, at least about or less than about 4
g, at least about or less than about 6 g, at least about or less
than about 8 g, at least about or less than about 10 g, at least
about or less than about 12 g, at least about or less than about 14
g, at least about or less than about 16 g, at least about or less
than about 18 g, at least about or less than about 20 g, at least
about or less than about 22 g, at least about or less than about 24
g, at least about or less than about 26 g, at least about or less
than about 28 g, at least about or less than about 30 g, at least
about or less than about 32 g, at least about or less than about 34
g, at least about or less than about 36 g, at least about or less
than about 38 g, at least about or less than about 40 g, at least
about or less than about 42 g, at least about or less than about 44
g, at least about or less than about 46 g, at least about or less
than about 48 g, at least about or less than about 50 g, at least
about or less than about 52 g, at least about or less than about 54
g, at least about or less than about 56 g, at least about or less
than about 58 g, or at least about or less than about 60 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 40 mg of at least
one proton pump inhibitor and at least about or less than about 2
g, at least about or less than about 4 g, at least about or less
than about 6 g, at least about or less than about 8 g, at least
about or less than about 10 g, at least about or less than about 12
g, at least about or less than about 14 g, at least about or less
than about 16 g, at least about or less than about 18 g, at least
about or less than about 20 g, at least about or less than about 22
g, at least about or less than about 24 g, at least about or less
than about 26 g, at least about or less than about 28 g, at least
about or less than about 30 g, at least about or less than about 32
g, at least about or less than about 34 g, at least about or less
than about 36 g, at least about or less than about 38 g, at least
about or less than about 40 g, at least about or less than about 42
g, at least about or less than about 44 g, at least about or less
than about 46 g, at least about or less than about 48 g, at least
about or less than about 50 g, at least about or less than about 52
g, at least about or less than about 54 g, at least about or less
than about 56 g, at least about or less than about 58 g, or at
least about or less than about 60 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 45 mg of at least one proton pump
inhibitor and at least about or less than about 2 g, at least about
or less than about 4 g, at least about or less than about 6 g, at
least about or less than about 8 g, at least about or less than
about 10 g, at least about or less than about 12 g, at least about
or less than about 14 g, at least about or less than about 16 g, at
least about or less than about 18 g, at least about or less than
about 20 g, at least about or less than about 22 g, at least about
or less than about 24 g, at least about or less than about 26 g, at
least about or less than about 28 g, at least about or less than
about 30 g, at least about or less than about 32 g, at least about
or less than about 34 g, at least about or less than about 36 g, at
least about or less than about 38 g, at least about or less than
about 40 g, at least about or less than about 42 g, at least about
or less than about 44 g, at least about or less than about 46 g, at
least about or less than about 48 g, at least about or less than
about 50 g, at least about or less than about 52 g, at least about
or less than about 54 g, at least about or less than about 56 g, at
least about or less than about 58 g, or at least about or less than
about 60 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 50 mg of at least one proton pump inhibitor and at least
about or less than about 2 g, at least about or less than about 4
g, at least about or less than about 6 g, at least about or less
than about 8 g, at least about or less than about 10 g, at least
about or less than about 12 g, at least about or less than about 14
g, at least about or less than about 16 g, at least about or less
than about 18 g, at least about or less than about 20 g, at least
about or less than about 22 g, at least about or less than about 24
g, at least about or less than about 26 g, at least about or less
than about 28 g, at least about or less than about 30 g, at least
about or less than about 32 g, at least about or less than about 34
g, at least about or less than about 36 g, at least about or less
than about 38 g, at least about or less than about 40 g, at least
about or less than about 42 g, at least about or less than about 44
g, at least about or less than about 46 g, at least about or less
than about 48 g, at least about or less than about 50 g, at least
about or less than about 52 g, at least about or less than about 54
g, at least about or less than about 56 g, at least about or less
than about 58 g, or at least about or less than about 60 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 55 mg of at least
one proton pump inhibitor and at least about or less than about 2
g, at least about or less than about 4 g, at least about or less
than about 6 g, at least about or less than about 8 g, at least
about or less than about 10 g, at least about or less than about 12
g, at least about or less than about 14 g, at least about or less
than about 16 g, at least about or less than about 18 g, at least
about or less than about 20 g, at least about or less than about 22
g, at least about or less than about 24 g, at least about or less
than about 26 g, at least about or less than about 28 g, at least
about or less than about 30 g, at least about or less than about 32
g, at least about or less than about 34 g, at least about or less
than about 36 g, at least about or less than about 38 g, at least
about or less than about 40 g, at least about or less than about 42
g, at least about or less than about 44 g, at least about or less
than about 46 g, at least about or less than about 48 g, at least
about or less than about 50 g, at least about or less than about 52
g, at least about or less than about 54 g, at least about or less
than about 56 g, at least about or less than about 58 g, or at
least about or less than about 60 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 60 mg of at least one proton pump
inhibitor and at least about or less than about 2 g, at least about
or less than about 4 g, at least about or less than about 6 g, at
least about or less than about 8 g, at least about or less than
about 10 g, at least about or less than about 12 g, at least about
or less than about 14 g, at least about or less than about 16 g, at
least about or less than about 18 g, at least about or less than
about 20 g, at least about or less than about 22 g, at least about
or less than about 24 g, at least about or less than about 26 g, at
least about or less than about 28 g, at least about or less than
about 30 g, at least about or less than about 32 g, at least about
or less than about 34 g, at least about or less than about 36 g, at
least about or less than about 38 g, at least about or less than
about 40 g, at least about or less than about 42 g, at least about
or less than about 44 g, at least about or less than about 46 g, at
least about or less than about 48 g, at least about or less than
about 50 g, at least about or less than about 52 g, at least about
or less than about 54 g, at least about or less than about 56 g, at
least about or less than about 58 g, or at least about or less than
about 60 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 65 mg of at least one proton pump inhibitor and at least
about or less than about 2 g, at least about or less than about 4
g, at least about or less than about 6 g, at least about or less
than about 8 g, at least about or less than about 10 g, at least
about or less than about 12 g, at least about or less than about 14
g, at least about or less than about 16 g, at least about or less
than about 18 g, at least about or less than about 20 g, at least
about or less than about 22 g, at least about or less than about 24
g, at least about or less than about 26 g, at least about or less
than about 28 g, at least about or less than about 30 g, at least
about or less than about 32 g, at least about or less than about 34
g, at least about or less than about 36 g, at least about or less
than about 38 g, at least about or less than about 40 g, at least
about or less than about 42 g, at least about or less than about 44
g, at least about or less than about 46 g, at least about or less
than about 48 g, at least about or less than about 50 g, at least
about or less than about 52 g, at least about or less than about 54
g, at least about or less than about 56 g, at least about or less
than about 58 g, or at least about or less than about 60 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 70 mg of at least
one proton pump inhibitor and at least about or less than about 2
g, at least about or less than about 4 g, at least about or less
than about 6 g, at least about or less than about 8 g, at
least about or less than about 10 g, at least about or less than
about 12 g, at least about or less than about 14 g, at least about
or less than about 16 g, at least about or less than about 18 g, at
least about or less than about 20 g, at least about or less than
about 22 g, at least about or less than about 24 g, at least about
or less than about 26 g, at least about or less than about 28 g, at
least about or less than about 30 g, at least about or less than
about 32 g, at least about or less than about 34 g, at least about
or less than about 36 g, at least about or less than about 38 g, at
least about or less than about 40 g, at least about or less than
about 42 g, at least about or less than about 44 g, at least about
or less than about 46 g, at least about or less than about 48 g, at
least about or less than about 50 g, at least about or less than
about 52 g, at least about or less than about 54 g, at least about
or less than about 56 g, at least about or less than about 58 g, or
at least about or less than about 60 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 75 mg of at least one proton pump
inhibitor and at least about or less than about 2 g, at least about
or less than about 4 g, at least about or less than about 6 g, at
least about or less than about 8 g, at least about or less than
about 10 g, at least about or less than about 12 g, at least about
or less than about 14 g, at least about or less than about 16 g, at
least about or less than about 18 g, at least about or less than
about 20 g, at least about or less than about 22 g, at least about
or less than about 24 g, at least about or less than about 26 g, at
least about or less than about 28 g, at least about or less than
about 30 g, at least about or less than about 32 g, at least about
or less than about 34 g, at least about or less than about 36 g, at
least about or less than about 38 g, at least about or less than
about 40 g, at least about or less than about 42 g, at least about
or less than about 44 g, at least about or less than about 46 g, at
least about or less than about 48 g, at least about or less than
about 50 g, at least about or less than about 52 g, at least about
or less than about 54 g, at least about or less than about 56 g, at
least about or less than about 58 g, or at least about or less than
about 60 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 80 mg of at least one proton pump inhibitor and at least
about or less than about 2 g, at least about or less than about 4
g, at least about or less than about 6 g, at least about or less
than about 8 g, at least about or less than about 10 g, at least
about or less than about 12 g, at least about or less than about 14
g, at least about or less than about 16 g, at least about or less
than about 18 g, at least about or less than about 20 g, at least
about or less than about 22 g, at least about or less than about 24
g, at least about or less than about 26 g, at least about or less
than about 28 g, at least about or less than about 30 g, at least
about or less than about 32 g, at least about or less than about 34
g, at least about or less than about 36 g, at least about or less
than about 38 g, at least about or less than about 40 g, at least
about or less than about 42 g, at least about or less than about 44
g, at least about or less than about 46 g, at least about or less
than about 48 g, at least about or less than about 50 g, at least
about or less than about 52 g, at least about or less than about 54
g, at least about or less than about 56 g, at least about or less
than about 58 g, or at least about or less than about 60 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 85 mg of at least
one proton pump inhibitor and at least about or less than about 2
g, at least about or less than about 4 g, at least about or less
than about 6 g, at least about or less than about 8 g, at least
about or less than about 10 g, at least about or less than about 12
g, at least about or less than about 14 g, at least about or less
than about 16 g, at least about or less than about 18 g, at least
about or less than about 20 g, at least about or less than about 22
g, at least about or less than about 24 g, at least about or less
than about 26 g, at least about or less than about 28 g, at least
about or less than about 30 g, at least about or less than about 32
g, at least about or less than about 34 g, at least about or less
than about 36 g, at least about or less than about 38 g, at least
about or less than about 40 g, at least about or less than about 42
g, at least about or less than about 44 g, at least about or less
than about 46 g, at least about or less than about 48 g, at least
about or less than about 50 g, at least about or less than about 52
g, at least about or less than about 54 g, at least about or less
than about 56 g, at least about or less than about 58 g, or at
least about or less than about 60 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 90 mg of at least one proton pump
inhibitor and at least about or less than about 2 g, at least about
or less than about 4 g, at least about or less than about 6 g, at
least about or less than about 8 g, at least about or less than
about 10 g, at least about or less than about 12 g, at least about
or less than about 14 g, at least about or less than about 16 g, at
least about or less than about 18 g, at least about or less than
about 20 g, at least about or less than about 22 g, at least about
or less than about 24 g, at least about or less than about 26 g, at
least about or less than about 28 g, at least about or less than
about 30 g, at least about or less than about 32 g, at least about
or less than about 34 g, at least about or less than about 36 g, at
least about or less than about 38 g, at least about or less than
about 40 g, at least about or less than about 42 g, at least about
or less than about 44 g, at least about or less than about 46 g, at
least about or less than about 48 g, at least about or less than
about 50 g, at least about or less than about 52 g, at least about
or less than about 54 g, at least about or less than about 56 g, at
least about or less than about 58 g, or at least about or less than
about 60 g of at least one bile acid sequestrant. In certain
embodiments, the dosage unit comprises at least about or less than
about 95 mg of at least one proton pump inhibitor and at least
about or less than about 2 g, at least about or less than about 4
g, at least about or less than about 6 g, at least about or less
than about 8 g, at least about or less than about 10 g, at least
about or less than about 12 g, at least about or less than about 14
g, at least about or less than about 16 g, at least about or less
than about 18 g, at least about or less than about 20 g, at least
about or less than about 22 g, at least about or less than about 24
g, at least about or less than about 26 g, at least about or less
than about 28 g, at least about or less than about 30 g, at least
about or less than about 32 g, at least about or less than about 34
g, at least about or less than about 36 g, at least about or less
than about 38 g, at least about or less than about 40 g, at least
about or less than about 42 g, at least about or less than about 44
g, at least about or less than about 46 g, at least about or less
than about 48 g, at least about or less than about 50 g, at least
about or less than about 52 g, at least about or less than about 54
g, at least about or less than about 56 g, at least about or less
than about 58 g, or at least about or less than about 60 g of at
least one bile acid sequestrant. In certain embodiments, the dosage
unit comprises at least about or less than about 100 mg of at least
one proton pump inhibitor and at least about or less than about 2
g, at least about or less than about 4 g, at least about or less
than about 6 g, at least about or less than about 8 g, at least
about or less than about 10 g, at least about or less than about 12
g, at least about or less than about 14 g, at least about or less
than about 16 g, at least about or less than about 18 g, at least
about or less than about 20 g, at least about or less than about 22
g, at least about or less than about 24 g, at least about or less
than about 26 g, at least about or less than about 28 g, at least
about or less than about 30 g, at least about or less than about 32
g, at least about or less than about 34 g, at least about or less
than about 36 g, at least about or less than about 38 g, at least
about or less than about 40 g, at least about or less than about 42
g, at least about or less than about 44 g, at least about or less
than about 46 g, at least about or less than about 48 g, at least
about or less than about 50 g, at least about or less than about 52
g, at least about or less than about 54 g, at least about or less
than about 56 g, at least about or less than about 58 g, or at
least about or less than about 60 g of at least one bile acid
sequestrant. In certain embodiments the at least one proton pump
inhibitor is omeprazole. In certain embodiments the at least one
proton pump inhibitor is esomeprazole. In certain embodiments the
at least one proton pump inhibitor is lansoprazole. In certain
embodiments the at least one proton pump inhibitor is pantoprazole.
In certain embodiments the at least one proton pump inhibitor is
rabeprazole. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole. In certain embodiments the at least one
bile acid sequestrant is cholestyramine. In certain embodiments the
at least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one bile acid sequestrant is
colesevelam-HCl. In certain embodiments the at least one bile acid
sequestrant is colestipol. In certain embodiments the at least one
proton pump inhibitor is omeprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is omeprazole and the at least one bile
acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is omeprazole and the at least one
bile acid sequestrant is colesevelam-HCl. In certain embodiments
the at least one proton pump inhibitor is omeprazole and the at
least one bile acid sequestrant is colestipol. In certain
embodiments the at least one proton pump inhibitor is esomeprazole
and the at least one bile acid sequestrant is cholestyramine. In
certain embodiments the at least one proton pump inhibitor is
esomeprazole and the at least one bile acid sequestrant is
colesevelam. In certain embodiments the at least one proton pump
inhibitor is esomeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is esomeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is lansoprazole and the at least one bile
acid sequestrant is cholestyramine. In certain embodiments the at
least one proton pump inhibitor is lansoprazole and the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one proton pump inhibitor is lansoprazole and the at
least one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is lansoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the at least one proton pump inhibitor is
pantoprazole and the at least one bile acid sequestrant is
cholestyramine. In certain embodiments the at least one proton pump
inhibitor is pantoprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is pantoprazole and the at least one bile
acid sequestrant is colesevelam-HCl. In certain embodiments the at
least one proton pump inhibitor is pantoprazole and the at least
one bile acid sequestrant is colestipol. In certain embodiments the
at least one proton pump inhibitor is rabeprazole and the at least
one bile acid sequestrant is cholestyramine. In certain embodiments
the at least one proton pump inhibitor is rabeprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is rabeprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
rabeprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is tenatoprazole and the at least one
bile acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is tenatoprazole and the at least
one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is tenatoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the dosage unit and daily dose are equivalent.
In various embodiments, the dosage unit is administered with food
at anytime of the day, without food at anytime of the day, with
food after an overnight fast (e.g. with breakfast), at bedtime
after a low fat snack. In various embodiments, the dosage unit is
administered once a day, twice a day, three times a day, four times
a day. The dosage unit can optionally comprise other agents such as
at least one antacid, at least one histamine Hz-receptor
antagonist, or combinations thereof.
In certain embodiments, the dosage unit comprises at least about or
less than about 5 mg of at least one proton pump inhibitor and at
least about or less than about 10 g, at least about or less than
about 20 g, at least about or less than about 30 g, at least about
or less than about 40 g, at least about or less than about 50 g, at
least about or less than about 60 g, at least about or less than
about 70 g, at least about or less than about 80 g, at least about
or less than about 90 g, at least about or less than about 100 g,
at least about or less than about 110 g, at least about or less
than about 120 g, at least about or less than about 130 g, at least
about or less than about 140 g, at least about or less than about
150 g, at least about or less than about 160 g, at least about or
less than about 170 g, at least about or less than about 180 g, at
least about or less than about 190 g, at least about or less than
about 200 g, at least about or less than about 210 g, at least
about or less than about 220 g, at least about or less than about
230 g, at least about or less than about 240 g, at least about or
less than about 250 g, at least about or less than about 260 g, at
least about or less than about 270 g, at least about or less than
about 280 g, at least about or less than about 290 g, or at least
about or less than about 300 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 10 mg of at least one proton pump
inhibitor and at least about or less than about 10 g, at least
about or less than about 20 g, at least about or less than about 30
g, at least about or less than about 40 g, at least about or less
than about 50 g, at least about or less than about 60 g, at least
about or less than about 70 g, at least about or less than about 80
g, at least about or less than about 90 g, at least about or less
than about 100 g, at least about or less than about 110 g, at least
about or less than about 120 g, at least about or less than about
130 g, at least about or less than about 140 g, at least about or
less than about 150 g, at least about or less than about 160 g, at
least about or less than about 170 g, at least about or less than
about 180 g, at least about or less than about 190 g, at least
about or less than about 200 g, at least about or less than about
210 g, at least about or less than about 220 g, at least about or
less than about 230 g, at least about or less than about 240 g, at
least about or less than about 250 g, at least about or less than
about 260 g, at least about or less than about 270 g, at least
about or less than about 280 g, at least about or less than about
290 g, or at least about or less than about 300 g of at least one
bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 15 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 20 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 25 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 30 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 35 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 40 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 45 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 50 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 55 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 60 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 65 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or
less than about 280 g, at least about or less than about 290 g, or
at least about or less than about 300 g of at least one bile acid
sequestrant. In certain embodiments, the dosage unit comprises at
least about or less than about 70 mg of at least one proton pump
inhibitor and at least about or less than about 10 g, at least
about or less than about 20 g, at least about or less than about 30
g, at least about or less than about 40 g, at least about or less
than about 50 g, at least about or less than about 60 g, at least
about or less than about 70 g, at least about or less than about 80
g, at least about or less than about 90 g, at least about or less
than about 100 g, at least about or less than about 110 g, at least
about or less than about 120 g, at least about or less than about
130 g, at least about or less than about 140 g, at least about or
less than about 150 g, at least about or less than about 160 g, at
least about or less than about 170 g, at least about or less than
about 180 g, at least about or less than about 190 g, at least
about or less than about 200 g, at least about or less than about
210 g, at least about or less than about 220 g, at least about or
less than about 230 g, at least about or less than about 240 g, at
least about or less than about 250 g, at least about or less than
about 260 g, at least about or less than about 270 g, at least
about or less than about 280 g, at least about or less than about
290 g, or at least about or less than about 300 g of at least one
bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 75 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 80 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 85 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 90 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 95 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments, the dosage unit
comprises at least about or less than about 100 mg of at least one
proton pump inhibitor and at least about or less than about 10 g,
at least about or less than about 20 g, at least about or less than
about 30 g, at least about or less than about 40 g, at least about
or less than about 50 g, at least about or less than about 60 g, at
least about or less than about 70 g, at least about or less than
about 80 g, at least about or less than about 90 g, at least about
or less than about 100 g, at least about or less than about 110 g,
at least about or less than about 120 g, at least about or less
than about 130 g, at least about or less than about 140 g, at least
about or less than about 150 g, at least about or less than about
160 g, at least about or less than about 170 g, at least about or
less than about 180 g, at least about or less than about 190 g, at
least about or less than about 200 g, at least about or less than
about 210 g, at least about or less than about 220 g, at least
about or less than about 230 g, at least about or less than about
240 g, at least about or less than about 250 g, at least about or
less than about 260 g, at least about or less than about 270 g, at
least about or less than about 280 g, at least about or less than
about 290 g, or at least about or less than about 300 g of at least
one bile acid sequestrant. In certain embodiments the at least one
proton pump inhibitor is omeprazole. In certain embodiments the at
least one proton pump inhibitor is esomeprazole. In certain
embodiments the at least one proton pump inhibitor is lansoprazole.
In certain embodiments the at least one proton pump inhibitor is
pantoprazole. In certain embodiments the at least one proton pump
inhibitor is rabeprazole. In certain embodiments the at least one
proton pump inhibitor is tenatoprazole. In certain embodiments the
at least one bile acid sequestrant is cholestyramine. In certain
embodiments the at least one bile acid sequestrant is colesevelam.
In certain embodiments the at least one bile acid sequestrant is
colesevelam-HCl. In certain embodiments the at least one bile acid
sequestrant is colestipol. In certain embodiments the at least one
proton pump inhibitor is omeprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is omeprazole and the at least one bile
acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is omeprazole and the at least one
bile acid sequestrant is colesevelam-HCl. In certain embodiments
the at least one proton pump inhibitor is omeprazole and the at
least one bile acid sequestrant is colestipol. In certain
embodiments the at least one proton pump inhibitor is esomeprazole
and the at least one bile acid sequestrant is cholestyramine. In
certain embodiments the at least one proton pump inhibitor is
esomeprazole and the at least one bile acid sequestrant is
colesevelam. In certain embodiments the at least one proton pump
inhibitor is esomeprazole and the at least one bile acid
sequestrant is colesevelam-HCl. In certain embodiments the at least
one proton pump inhibitor is esomeprazole and the at least one bile
acid sequestrant is colestipol. In certain embodiments the at least
one proton pump inhibitor is lansoprazole and the at least one bile
acid sequestrant is cholestyramine. In certain embodiments the at
least one proton pump inhibitor is lansoprazole and the at least
one bile acid sequestrant is colesevelam. In certain embodiments
the at least one proton pump inhibitor is lansoprazole and the at
least one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is lansoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the at least one proton pump inhibitor is
pantoprazole and the at least one bile acid sequestrant is
cholestyramine. In certain embodiments the at least one proton pump
inhibitor is pantoprazole and the at least one bile acid
sequestrant is colesevelam. In certain embodiments the at least one
proton pump inhibitor is pantoprazole and the at least one bile
acid sequestrant is colesevelam-HCl. In certain embodiments the at
least one proton pump inhibitor is pantoprazole and the at least
one bile acid sequestrant is colestipol. In certain embodiments the
at least one proton pump inhibitor is rabeprazole and the at least
one bile acid sequestrant is cholestyramine. In certain embodiments
the at least one proton pump inhibitor is rabeprazole and the at
least one bile acid sequestrant is colesevelam. In certain
embodiments the at least one proton pump inhibitor is rabeprazole
and the at least one bile acid sequestrant is colesevelam-HCl. In
certain embodiments the at least one proton pump inhibitor is
rabeprazole and the at least one bile acid sequestrant is
colestipol. In certain embodiments the at least one proton pump
inhibitor is tenatoprazole and the at least one bile acid
sequestrant is cholestyramine. In certain embodiments the at least
one proton pump inhibitor is tenatoprazole and the at least one
bile acid sequestrant is colesevelam. In certain embodiments the at
least one proton pump inhibitor is tenatoprazole and the at least
one bile acid sequestrant is colesevelam-HCl. In certain
embodiments the at least one proton pump inhibitor is tenatoprazole
and the at least one bile acid sequestrant is colestipol. In
certain embodiments the dosage unit and daily dose are equivalent.
In various embodiments, the dosage unit is administered with food
at anytime of the day, without food at anytime of the day, with
food after an overnight fast (e.g. with breakfast), at bedtime
after a low fat snack. In various embodiments, the dosage unit is
administered once a day, twice a day, three times a day, four times
a day. The dosage unit can optionally comprise other agents such as
at least one antacid, at least one histamine Hz-receptor
antagonist, or combinations thereof.
[0183] Kits
[0184] The compounds and pharmaceutical formulations described
herein may be contained in a kit. The kit may include single or
multiple doses of one or more agent, each packaged or formulated
individually, or single or multiple doses of two or more agents
packaged or formulated in combination. Thus, one or more agents can
be present in a first container, and the kit can optionally include
one or more agents in a second container. The container or
containers are placed within a package, and the package can
optionally include administration or dosage instructions in the
form of a label on the package or in the form of an insert included
in the packaging of the kit. A kit can include additional
components such as syringes or other means for administering the
agents as well as diluents or other means for formulation.
[0185] Thus, the kits can comprise: a) a pharmaceutical composition
comprising at least one bile acid sequestrant and a
pharmaceutically acceptable carrier, vehicle (e.g., a
gastric-retention vehicle) or diluent; and b) a container or
packaging. In another embodiment, the kit can comprise: a) a
pharmaceutical composition comprising at least on bile acid
sequestrant, at least one proton pump inhibitor, and a
pharmaceutically acceptable carrier, vehicle (e.g. a
gastric-retention vehicle), or diluent; and b) a container or
packaging. The kits may optionally comprise instructions describing
a method of using the pharmaceutical compositions in one or more of
the methods described herein (e.g., preventing or treating
dyspepsia, heartburn, erosive esophagitis, GERD, peptic ulcer,
esophagitis, Barrett's esophagus, and esophageal adenocarcinoma).
The kit may optionally comprise a second pharmaceutical composition
comprising any of at least one antacid, at least one histamine
Hz-receptor antagonist, at least one GABA-B agonist, at least one
prodrug of a GABA-B agonist, at least one protease inhibitor, or
combinations thereof and a pharmaceutically acceptable carrier,
vehicle or diluent. The pharmaceutical composition comprising the
at least one bile acid sequestrant (or the at least one bile acid
sequestrant and at least one proton pump inhibitor), and the second
pharmaceutical composition contained in the kit may be optionally
combined in the same pharmaceutical composition.
[0186] A kit includes a container or packaging for containing the
pharmaceutical compositions and may also include divided containers
such as a divided bottle or a divided foil packet. The container
can be, for example a paper or cardboard box, a glass or plastic
bottle or jar, a re-sealable bag (for example, to hold a "refill"
of tablets for placement into a different container), or a blister
pack with individual doses for pressing out of the pack according
to a therapeutic schedule. It is feasible that more than one
container can be used together in a single package to market a
single dosage form. For example, tablets may be contained in a
bottle which is in turn contained within a box.
[0187] An example of a kit is a so-called blister pack. Blister
packs are well known in the packaging industry and are being widely
used for the packaging of pharmaceutical unit dosage forms
(tablets, capsules, and the like). Blister packs generally consist
of a sheet of relatively stiff material covered with a foil of a
preferably transparent plastic material. During the packaging
process, recesses are formed in the plastic foil. The recesses have
the size and shape of individual tablets or capsules to be packed
or may have the size and shape to accommodate multiple tablets
and/or capsules to be packed. Next, the tablets or capsules are
placed in the recesses accordingly and the sheet of relatively
stiff material is sealed against the plastic foil at the face of
the foil which is opposite from the direction in which the recesses
were formed. As a result, the tablets or capsules are individually
sealed or collectively sealed, as desired, in the recesses between
the plastic foil and the sheet. Preferably the strength of the
sheet is such that the tablets or capsules can be removed from the
blister pack by manually applying pressure on the recesses whereby
an opening is formed in the sheet at the place of the recess. The
tablet or capsule can then be removed via said opening.
[0188] It maybe desirable to provide a written memory aid
containing information and/or instructions for the physician,
pharmacist or subject regarding when the medication is to be taken.
A "daily dose" can be a single tablet or capsule or several tablets
or capsules to be taken on a given day. When the kit contains
separate compositions, a daily dose of one or more compositions of
the kit can consist of one tablet or capsule while a daily dose of
another one or more compositions of the kit can consist of several
tablets or capsules. A kit can take the form of a dispenser
designed to dispense the daily doses one at a time in the order of
their intended use. The dispenser can be equipped with a
memory-aid, so as to further facilitate compliance with the
regimen. An example of such a memory-aid is a mechanical counter
which indicates the number of daily doses that have been dispensed.
Another example of such a memory-aid is a battery-powered
micro-chip memory coupled with a liquid crystal readout, or audible
reminder signal which, for example, reads out the date that the
last daily dose has been taken and/or reminds one when the next
dose is to be taken.
[0189] Various patent and/or scientific literature references have
been referred to throughout this application. The disclosures of
these publications in their entireties are hereby incorporated by
reference as if written herein. In view of the above description
and the examples below, one of ordinary skill in the art will be
able to practice the disclosure as claimed without undue
experimentation. The foregoing will be better understood with
reference to the following Examples that detail certain procedures
for the preparation of formulations according to the present
disclosure. All references made to these Examples are for the
purposes of illustration. The following Examples should not be
considered exhaustive, but merely illustrative of only a few of the
many embodiments contemplated by the present disclosure.
Examples
Example 1. Effects of Bile Acid Sequestrant Alone and in
Combination, on Esophageal Epithelial Cells
[0190] Epithelial cells are isolated from normal human esophagus
and Barrett's esophagus samples (e.g. biopsies) and established in
monolayer cell cultures as described in Burg-Kurland et al. (1986)
Methods in Cell Science 10:227-232 or cultured as described in
Trier, J. S. (1980) Methods Cell Biol. 18:365-384. Barrett's
Esophagus is induced or exacerbated by the addition of bile
acid(s), stomach acid(s), and/or other acids or acidified media
(for example as in Fitzgerald et al. (1996) J Clin Invest
98:2120-8). Acid exposure is continuous or as a timed pulse (e.g. 1
hour). Test article (e.g. vehicle alone, proton pump inhibitor,
bile acid sequestrant, proton pump inhibitor and bile acid
sequestrant) at various doses (for example, as described in the
present application) is added either before, simultaneously with,
or after acid addition. Barrett's Esophagus development is
monitored visually by microscope by the transformation of squamous
cells to columnar cells. Cell proliferation is determined by
tritiated thymidine incorporation and proliferating cell nuclear
antigen expression. Cell differentiation is determined by villin
expression (see Fitzgerald et al. supra).
Example 2: Effects of Bile Acid Sequestrant, Alone and in
Combination, on in Vivo Model of Barrett's Esophagus
[0191] Test article (e.g. vehicle alone, proton pump inhibitor,
bile acid sequestrant, proton pump inhibitor and bile acid
sequestrant) at various doses (for example, as described in the
present application) is evaluated for effects on 2 different rodent
models of Barrett's Esophagus, for example as described in Buskens
et al. (2006) J Surg Res. 135:337-44.
[0192] Although the foregoing disclosure has been described and
depicted in terms of certain preferred embodiments, other specific
embodiments may be effected by those skilled in the art to
accomplish the same objectives and without departing from the true
spirit of the scope of the present disclosure. Accordingly, the
scope of the Applicant's disclosure is to be determined by
reference to the attached claims, which are not limited to any of
the particular embodiments disclosed herein.
* * * * *