Generic Name: Misoprostol
Class: Prostaglandins
ATC Class: A02BB01
VA Class: GA309
Chemical Name: 11α,13E)-(±)-11,16-Dihydroxy-16-methyl-9-oxo-prost-13-en-1-oic acid methyl ester
Molecular Formula: C22H38O5
CAS Number: 59122-46-2
Introduction
Gastric antisecretory agent with protective effects on the gastroduodenal mucosa;1 2 3 13 15 16 25 26 27 31 35 37 47 57 60 72 76 77 78 79 80 84 85 86 87 88 89 91 94 95 127 a synthetic analog of prostaglandin E1 (alprostadil).1 5 10 11 13 20 25 26 27 31 55 76 78 85 95
Uses for Cytotec
Prevention of NSAIA-induced Ulcers
Treatment to reduce the risk of NSAIA-induced gastric ulcers in patients at high risk (e.g., concomitant debilitating disease, geriatric patients, history of upper GI ulcer) of developing complications (e.g., bleeding, perforation, death) from these ulcers.1 5 56 61 67 68 70 85 95 96 135 233
Not recommended for use in women of childbearing potential unless the woman is at high risk of developing gastric ulcers or of complications resulting from NSAIA-induced gastric ulcers.1
Gastric Ulcer
Short-term treatment of active, benign, gastric ulcer†;2 55 58 72 76 85 87 however, not considered a drug of choice.140
Maintenance treatment following healing of active gastric ulcer to reduce ulcer recurrence†.72
Duodenal Ulcer
Short-term treatment of endoscopically or radiographically confirmed active duodenal ulcer†;2 23 55 78 79 80 83 84 85 86 89 91 92 93 94 however, not considered a drug of choice.140
Termination of Pregnancy
Use as an adjunct to mifepristone for medical termination of an intrauterine pregnancy.234 (See Pregnancy under Cautions.)
Labor Induction
Treatment to improve cervical inducibility (cervical “ripening”) in appropriately selected pregnant women with unfavorable cervices with a medical or obstetric need for labor induction†.235 237 238 However, avoid such use in women with prior uterine surgery or cesarean section because of the risk of possible uterine rupture.235 237 238
Postpartum Hemorrhage
Prevention or treatment of serious postpartum hemorrhage† in the presence of uterine atony.1 237
Cytotec Dosage and Administration
Administration
Administer orally.1 2 3 4 5
Also has been administered intravaginally†, using tablets formulated for oral administration.1 235 237 238
Oral Administration
Administer in divided doses after meals and at bedtime.1 3
Avoid concomitant administration with a magnesium-containing or other laxative antacid to minimize the incidence of misoprostol-induced diarrhea.1 (See GI Effects under Cautions and also see Interactions.)
Dosage
Available as mifoprostol; dosage expressed in terms of mifoprostol.1
Adults
Prevention of NSAIA-Induced Ulcers
Oral
200 mcg 4 times daily.1 56 57 59 76 81 95 May reduce dosage to 100 mcg 4 times daily if higher dosage is not well tolerated;1 61 70 however, reduced dosage may be less effective.1 61 67 73 95 Alternatively, 200 mcg twice daily.1 60 Continue therapy for the duration of NSAIA therapy.1
Gastric Ulcer†
Oral
100 or 200 mcg 4 times daily for 8 weeks.2 55 58 72 76 87
Duodenal Ulcer†
Oral
100 or 200 mcg 4 times daily or 400 mcg twice daily for 4–8 weeks.2 23 55 78 80 84 89 91 93
Termination of Pregnancy
Oral
400 mcg administered orally on day 3 (2 days after mifepristone administration) unless abortion has occurred and has been confirmed by clinical examination or ultrasonographic scan.234 See Mifepristone 76:00.
Induction of Labor†
Intravaginal
Initially, 25 mcg (¼ of a 100-mcg oral tablet).235 237 238 Subsequently, 25-mcg every 3–6 hours.235 237 238
Prescribing Limits
Adults
Induction of Labor†
Intravaginal
Maximum 25 mcg.235 237 238 Subsequently, maximum 25-mcg every 3–6 hours.235 237 238 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Special Populations
Renal Impairment
Routine dosage reduction not required;1 5 however, dosage can be reduced if not tolerated.1 5
Geriatric Patients
Routine dosage reduction not required;1 5 however, dosage can be reduced if not tolerated.1 5
Cautions for Cytotec
Contraindications
Warnings/Precautions
Warnings
Fetal/Neonatal Morbidity and Mortality
Possible teratogenic and abortifacient effects; possible serious fetal harm when administered to pregnant women.1 5 70 Possible uterine contractions and uterine bleeding and total or partial expulsion of the products of conception in pregnant women.1 3 23 55 Spontaneous abortions may result in dangerous uterine bleeding, premature birth, or birth defects.1 5 Possible congenital abnormalities (e.g., skull defects, cranial nerve palsies, facial malformations, and limb defects); sometimes associated with fetal death.1
Do not use in pregnant women for reducing the risk of NSAIA-induced gastric ulcers.1 (See Contraindications under Cautions.) Do not initiate therapy in women of childbearing potential until pregnancy is excluded and other necessary precautions (effective contraception) are ensured.1 5 13 64 70 85 Initiate therapy only after determining that patient is reliable and able to comply with effective contraceptive measures.1 Perform a reliable, blood pregnancy test within 2 weeks prior to beginning therapy.1 Initiate therapy on the second or third day of the next normal menstrual cycle, after a negative pregnancy test is reported.1 (See Pregnancy and also see Lactation under Cautions.)
If inadvertently administered during pregnancy or if the patient becomes pregnant while receiving the drug, discontinue therapy and inform patient of the potential hazard to the fetus.1
Intravaginal use may result in uterine hyperstimulation, uterine tetany, uterine rupture, amniotic fluid embolism, pelvic pain, retained placenta, severe genital bleeding, shock, fetal bradycardia, and fetal and maternal death, especially with dosages >25 mcg.1 237 (See Prescribing Limits under Dosage and Administration.) Risk of uterine rupture increases with advancing gestational age, prior uterine surgery (including cesarean delivery), and grand multiparity.1 237 Intravaginal use is not recommended in patients with a previous cesarean delivery or prior major uterine surgery.237
Sensitivity Reactions
Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylaxis, reported.1
General Precautions
GI Effects
Possible diarrhea; 1 3 5 15 22 23 55 56 57 58 59 61 64 76 78 79 80 81 84 85 86 89 91 92 93 121 151 usually apparent after about 2 weeks of therapy.1 Generally is self-limiting,1 58 61 78 80 85 89 resolving within about a week after onset.1 61 Possible increased risk of profound (e.g., voluminous, watery) and life-threatening diarrhea in patients with inflammatory bowel disease.1 151 Use with extreme caution in these patients; careful monitoring recommended.1 151 Careful monitoring recommended in patients prone to dehydration or in whom its consequences would be dangerous.1 Administer in divided doses after meals and at bedtime;1 3 avoid concomitant administration with a magnesium-containing or other laxative antacid to minimize diarrhea.1 (See Interactions.)
Cardiovascular Effects
Chest pain, edema, diaphoresis, hypotension, hypertension, arrhythmia, phlebitis, increased serum concentrations of cardiac enzymes, syncope, MI (some fatal), and thromboembolic events (e.g., pulmonary embolism, arterial thrombosis, cerebrovascular accident) reported; causal relationship to drug not established.1 Use with caution in patients with preexisting cardiovascular disease.1
Use of Fixed Combination
When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.
Specific Populations
Pregnancy
Category X. (See Fetal/Neonatal Morbidity and Mortality and also see Contraindications under Cautions.)
Ruptured ectopic pregnancy (rarely resulting in fatal hemorrhage); serious, rarely fatal, bacterial (e.g., Clostridium sordellii) infection and sepsis; or MI reported in a limited number of patients receiving intravaginal misoprostol with mifepristone for termination of pregnancy; causal relationship to regimen not established.234 241 242 244
Lactation
Not known whether misoprostol is distributed into milk.1 Use not recommended.1
Pediatric Use
Safety and efficacy not established in children <18 years of age.1
Geriatric Use
No substantial differences in safety relative to younger adults.1
Renal Impairment
Possible increased half-life,1 3 peak plasma misoprostol acid concentrations, and areas under the plasma concentration-time curves (AUCs).1 3 (See Special Populations under Pharmacokinetics.)
Common Adverse Effects
Diarrhea,1 3 5 15 22 23 55 56 57 58 59 61 64 76 78 79 80 81 84 85 86 89 91 92 93 121 151 abdominal pain.1 5 22 32 55 56 57 61 76 81 91 92 121
Interactions for Cytotec
Drugs Metabolized by Hepatic Microsomal Enzymes
Pharmacokinetic interaction unlikely.1 3 5 41 126 127
Specific Drugs and Foods
Drug or Food
|
Interaction
|
Comments
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|---|
Aspirin
|
Possible decreased AUCs of aspirin1 127
|
Interaction not clinically important1 5 56 127 129
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Cyclosporine
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Possible beneficial renal effects127 129 144 149 and reversal of cyclosporine-induced nephrotoxicity134 138
|
|
Food and antacids
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Potential decreased rate of absorption of misoprostol, decreased peak plasma concentrations of misoprostol acid1 3 5 95 and decreased oral bioavailability of misoprostol1 5
Magnesium-containing antacids may increase the incidence of misoprostol-induced diarrhea1
|
Avoid concomitant administration of a magnesium-containing or other laxative antacid1 93
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NSAIAs (ibuprofen, piroxicam, diclofenac)
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Pharmacokinetic interactions unlikely 1 5 127 129
|
|
Cytotec Pharmacokinetics
Absorption
Bioavailability
Rapidly and almost completely absorbed from the GI tract;1 2 5 41 42 45 95 88% of a dose is absorbed.45
Onset
Following oral administration, inhibition of gastric acid secretion reaches a maximum within 60–90 minutes.1 5 12 24 36 95
Duration
Following oral administration, inhibition of gastric acid secretion persists for at least 3 hours.1 5 12 24 36 95 Duration is directly related to dose.1 2 12 24 33 46 55 109
Food
Food and antacids decrease the rate of absorption of misoprostol, resulting in delayed and decreased peak plasma concentrations.1 3 95 131
Special Populations
Increased peak plasma misoprostol acid concentrations and AUCs in patients with renal impairment.1 3 In geriatric patients, possible increased AUCs;1 3 5 43 131 however, peak plasma concentrations are not affected.3 43 131
Distribution
Extent
Distribution into human body tissues and fluids has not been fully characterized.2 5 41 Not known whether misoprostol and/or misoprostol acid cross the placenta5 or are distributed into milk in humans.1 5
Plasma Protein Binding
Approximately 80–90%.1 2 41
Elimination
Metabolism
Rapidly and extensively metabolized to misoprostol acid (the free acid),1 2 5 41 42 43 45 95 at least in part in the GI tract.46 143 Misoprostol acid undergoes extensive, rapid metabolism1 2 3 41 to form inactive metabolites.1 45 127
Elimination Route
Excreted in urine (73%)1 45 100 mainly as metabolites and in feces (15%) via biliary excretion2 45 .
Half-life
Biphasic; half-life of free acid is 20–40 minutes.1 5 41 131
Special Populations
In patients with renal impairment, possible increased half-life.1 3
Stability
Storage
Oral
Tablets
Well-closed containers4 a≤25°C.1 5
ActionsActions
Inhibits gastric acid secretion and protects the gastroduodenal mucosa.1 2 3 15 16 25 26 27 31 35 37 47 57 60 77 85
Exhibits substantial dose-related1 2 12 24 33 46 55 109 inhibitory effects on basal, nocturnal, and food- or histamine-stimulated gastric acid secretion1 2 6 12 14 24 32 36 95 via a direct action at the parietal cells.1 2 3 4 5 9 14 20 24 33 64
Protective effect may result from increased mucus secretion,1 2 3 5 10 23 25 26 27 33 35 51 95 increased bicarbonate secretion from nonparietal cells,1 2 3 5 10 23 25 26 31 33 35 53 95 enhancement or maintenance of blood flow of the mucosa (possibly via direct vasodilation),2 9 10 17 25 26 33 35 95 protection of submucosal cell proliferation,23 26 stabilization of mucosal membrane systems,23 25 35 prevention of mucosal barrier disruption,2 10 33 35 enhancement of transmucosal diffusion potential,2 117 and inhibition or reduction of back diffusion of hydrogen ions into the mucosa.2 3 33
Stimulates intestinal fluid secretion and effects motility.137
Increases the amplitude and frequency of uterine contractions and stimulates uterine bleeding and total or partial expulsion of uterine contents in pregnant women.1 3 23 55
Advice to Patients
Importance of providing patient a copy of manufacturer’s patient information.1 Patients should read the patient information before initiating misoprostol therapy and every time the prescription is refilled.1
Risk of serious fetal harm if administered in pregnant women.1 Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus.1 5 23 95 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Importance of informing patient that sharing the drug with another individual, particularly a woman of childbearing potential, could be hazardous.1
Importance of promptly informing clinicians if they have problems with or questions about misoprostol.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements.1
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Misoprostol
Routes
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Dosage Forms
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Strengths
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Brand Names
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Manufacturer
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|---|
Oral
|
Tablets
|
100 mcg*
|
Cytotec
|
Pfizer
|
|
|
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Misoprostol Tablets
|
Teva
|
|
|
200 mcg*
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Cytotec
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Pfizer
|
|
|
|
Misoprostol Tablets
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Teva
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Misoprostol Combinations
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Oral
|
Tablets, enteric-coated core, film-coated
|
200 mcg Misoprostol outer layer with 50 mg Diclofenac Sodium enteric-coated core
|
Arthrotec (with povidone)
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Pfizer
|
|
|
200 mcg Misoprostol outer layer with 75 mg Diclofenac Sodium enteric-coated core
|
Arthrotec (with povidone)
|
Pfizer
|
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Arthrotec 50 50-200MG-MCG Tablets (PFIZER U.S.): 60/$178.68 or 180/$523.27
Arthrotec 75 75-200MG-MCG Tablets (PFIZER U.S.): 60/$186.32 or 180/$530.89
Cytotec 100MCG Tablets (PFIZER U.S.): 60/$89.99 or 180/$245.96
Cytotec 200MCG Tablets (PFIZER U.S.): 60/$119.99 or 180/$339.98
Misoprostol 100MCG Tablets (IVAX PHARMACEUTICALS INC.): 60/$39.99 or 180/$106.99
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 01, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
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20. Tsai BS, Kessler LK, Schoenhard G et al. Demonstration of specific E-type prostaglandin receptors using enriched preparations of canine parietal cells and [3H] misoprostol free acid. Am J Med. 1987; 83(Suppl 1A):9-14. [PubMed 2887113]
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22. Ryan JR, Vargas R, Clay GA et al. Role of misoprostol in reducing aspirin-induced gastrointestinal blood loss in arthritic patients. Am J Med. 1987; 83(Suppl 1A):41-4. [IDIS 232701] [PubMed 3113245]
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27. Hunt JN, Smith JL, Jiang CL et al. Effect of synthetic prostaglandin E1 analog on aspirin-induced gastric bleeding and secretion. Dig Dis Sci. 1983; 28:897-902. [IDIS 177262] [PubMed 6604619]
28. McGuigan JE, Chang Y, Dajani EZ. Effect of misoprostol, an antiulcer prostaglandin, on serum gastrin in patients with duodenal ulcer. Dig Dis Sci. 1986; 31(Suppl):120-5S.
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33. Bauer RF. Misoprostol preclinical pharmacology. Dig Dis Sci. 1985; 30(Suppl):118-25S.
34. Agrawal NM, Godiwala T, Arimura A et al. Cytoprotection by a synthetic prostaglandin against ethanol-induced gastric mucosal damage. Gastrointest Endosc. 1986; 32:67-70. [PubMed 3086177]
35. Miller TA. Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am J Physiol. 1983; 245:G601-23. [PubMed 6195926]
36. Ramage JK, Denton A, Williams JG. Inhibition of food stimulated acid secretion by misoprostol, an orally active synthetic E1 analogue prostaglandin. Br J Clin Pharmacol. 1985; 19:9-12. [IDIS 196422] [PubMed 3919751]
37. Gullikson G, Anglin C, Kessler L et al. Misoprostol prevents aspirin-induced damage in canine Heidenhain pouches. Gastroenterology. 1983; 84(5 Part 2):1176.
38. Moore JG, Alazraki N, Clay GD. Effect of synthetic prostaglandin E1 analog on gastric emptying of meals in man. Dig Dis Sci. 1986; 31: 16-20. [IDIS 210928] [PubMed 3079695]
39. Konturek SJ, Pawlik W. Physiology and pharmacology of prostaglandins. Dig Dis Sci. 1986; 31(Suppl):6-19S.
40. Salmon PR, Barton T. Comparative inhibition of coffee-induced gastric acid secretion employing misoprostol and cimetidine. Dig Dis Sci. 1986; 31(Suppl):55-62S.
41. Schoenhard G, Oppermann J, Kohn FE. Metabolism and pharmacokinetic studies of misoprostol. Dig Dis Sci. 1985; 30(Suppl):126-8S.
42. Leese PT, Karim A, Rozek L. Technical and pharmacological considerations in evaluating misoprostol pharmacokinetic data. Dig Dis Sci. 1986; 31(Suppl):147S. [IDIS 212240] [PubMed 3731990]
43. Karim A, Burns TS, Miller MS et al. Pharmacokinetics and safety of the anti-ulcer prostaglandin mosiprostol in elderly male subjects. Clin Pharmacol Ther. 1987; 41:205.
44. Karim A, Rozek LF, Leese PT. Absorption of misoprostol (Cytotec), an antiulcer prostaglandin, or aspirin is not affected when given concomitantly to healthy human subjects. Gastroenterology. 1987; 92(5 Part 2):1742.
45. Karim A. Antiulcer prostaglandin misoprostol: single and multiple dose pharmacokinetic profile. Prostaglandins. 1989; 33(Suppl):40-50.
46. Tsai BS, Kessler L, Egofske P et al. Antisecretory activity and metabolism of misoprostol in isolated canine parietal cells. Dig Dis Sci. 1986; 31(Suppl):145-50S. [IDIS 212021] [PubMed 3080277]
47. Bauer RF, Bianchi RG, Casler J et al. Comparative mucosal protective properties of misoprostol, cimetidine, and sucralfate. Dig Dis Sci. 1986; 31(Suppl):81-5S.
48. Leung FW, Miller JC, Guth PH. Dissociated effects of misoprostol on gastric acid secretion and mucosal blood flow. Dig Dis Sci. 1986; 31(Suppl): 86-90S.
49. Smedfors B, Johansson C. Stimulation of duodenal bicarbonate secretion by misoprostol. Dig Dis Sci. 1986; 31(Suppl):96-100S.
50. Liss RH, Letourneau RJ, Schepis JP. Evaluation of cytoprotection against ethanol-induced injury in gastric mucosa pretreated with misoprostol, cimetidine, or placebo. Dig Dis Sci. 1986; 31(Suppl):108-14S.
51. Wilson DE, Quadros E, Rajapaksa T et al. Effects of misoprostol on gastric acid and mucus secretion in man. Dig Dis Sci. 1986; 31(Suppl): 126-9S. [IDIS 212234] [PubMed 3080283]
52. Rainsford KD. The effects of aspirin and other non-steroid anti-inflammatoryanalgesic drugs on gastro-intestinal mucus glycoprotein biosynthesis in vivo: relationship to ulcerogen
