Dose-response, meal-stimulated gastric antisecretory study of prostaglandin E1 analog, misoprostol, in man

Digestive Diseases and Sciences - Tập 33 - Trang 298-302 - 1988
Glenn R. Davis1,2, John S. Fordtran1,2, Esam Z. Dajani1,2
1Department of Internal Medicine, Section of Gastroenterology, Baylor University Medical Center, Dallas
2G.D. Searle and Company, Chicago

Tóm tắt

In a randomized, double-blind, crossover trial, the effects of 50-, 100-, and 200- Μg doses of misoprostol on meal-stimulated gastric acid secretion were compared with placebo in 16 healthy male subjects. Compared with placebo, the 100- and 200- Μg doses produced significant reductions in acid output for 2 and 3 hr, respectively, following the test meal (P=0.05). Misoprostol did not influence either the fasting or postprandial serum gastrin levels as compared with placebo. No adverse experiences were reported by any of the subjects. One subject experienced a transient rise in SGPT as compared with baseline, which may have been due to ethanol intake. This study provides a scientific rationale on which to base additional trials of misoprostol in patients with disease related to gastric acid production.

Tài liệu tham khảo

Higgins CB, Braunwald E: The prostaglandins. Biochemical, physiologic and clinical considerations. Am J Med 53:92–112, 1972 Weeks JR: Prostaglandins. Annu Rev Pharmacol 12:317–336, 1972 Pitt B, Shea MJ, Romson JL, Lucchesi BR: Prostaglandins and prostaglandin inhibitors in ischemic heart disease. Ann Intern Med 99:83–92, 1983 Wilson DE, Levine RA: The effect of prostaglandin E1 on canine gastric acid secretion and gastric mucosal blood flow. Dig Dis Sci 17:527–532, 1972 Classen M, Koch H, Bickhardt J, Topf G, Demling L: The effect of prostaglandin E1 on the pentagastin-stimulated gastric secretion in man. Digestion 4:333–344, 1971 Robert A, Nezamis JE, Phillips JP: Inhibition of gastric secretion by prostaglandins. Am J Dig Dis 12:1073–1076, 1967 Robert A, Nezamis JE, Lancaster C, Hanchar AJ: Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 77:433–443, 1979 Robert A: Cytoprotection by prostaglandins. Gastroenterology 77:761–767, 1979 Dajani EZ, Driskill DR, Bianchi RG, Collins PW, Pappo R: SC-29333: A potent inhibitor of canine gastric secretion. Dig Dis Sci 21:1049–1057, 1976 Dajani EZ, Callison DA, Bianchi RG, Driskill DR: Gastric antisecretory effects of E prostaglandins in rhesus monkeys. Dig Dis Sci 21:1020–1028, 1976 Colton DG, Driskill DR, Phillips EL, Poy P, Dajani EZ: Effect of SC-29333, an inhibitor of gastric secretion, on canine gastric mucosal blood flow and serum gastrin levels. Arch Int Pharmacodyn 236:86–95, 1978 Larsen KR, Jensen NF, David EK, Jensen JC, Moody FG: The cytoprotective effects of (±)15-deoxy-16-α,Β-hydroxy 16-methyl PGE1 methyl ester (SC-29333) versus aspirin shock gastric ulcerogenesis in the dog. Prostaglandins 21(suppl):119–124, 1981 Hunt JN, Smith JL, Jiang CL, Kessler L: Effect of synthetic prostaglandin E1 analog on aspirin-induced gastric bleeding and secretion. Dig Dis Sci 28:897–902, 1983 Akdamar K, Agrawal NM, Ertan A: Inhibition of nocturnal gastric secretion in normal human volunteers by misoprostol: A synthetic prostaglandin E1 methyl ester analog. Am J Gastroenterology 77:902–904, 1982 Agrawal NM, Godiwala T, Arimura A, Dajani EZ: Cytoprotection by a synthetic prostaglandin against ethanol-induced gastric mucosal damage. A double-blind endoscopic study in human subjects. Gastrointest Endosc 32:67–70, 1986 Steiner JA: Misoprostol clinical pharmacology: Establishment of activity in man. Dig Dis Sci 30:136S-141S, 1985 Herting RL: Overview of misoprostol clinical experience. Dig Dis Sci 31:47S-54S, 1986 McGuigan JE: Radioimmunoassay of gastrin.In Manual of Clinical Immunology. NR Rose, H Friedman (eds). Washington, American Society for Microbiology, 1976, pp 182–189 Winer BJ: Statistical Principles in Experimental Design, 2nd ed. New York, McGraw-Hill, 1971, pp 375–378, 544 Gugler R, Fuchs G, Dieckmann M, Somogyi AA: Cimetidine plasma concentration response relationships. Clin Pharmacol Ther 29:744–748, 1981 Konturek SJ, Obtulowicz W, Kwiecien N, Sito E, Olesky J, Miszczuk-Jamska B: Effect of ranitidine, a new H2-antagonist, on gastric and pancreatic secretion in duodenal ulcer patients. Dig Dis Sci 25:737–743, 1980 Dajani EZ, Callison DA, Bertermann RE: Effects of E-prostaglandins on canine gastric potential difference. Dig Dis Sci 23:436–442, 1978 Colton DG, Callison DA, Dajani EZ: Effects of SC-29333 and aspirin on gastric ionic fluxes and potential difference. J Pharmacol Exp Ther 210:283–288, 1979 Bauer RF: Misoprostol preclinical pharmacology. Dig Dis Sci 30:118S-125S, 1985 Wilson DE, Quedros E, Rajapaksa T, Adams A, Noar M: Effects of misoprostol on gastric acid and mucus secretion in man. Dig Dis Sci 31:126S-129S, 1986 Garner A, Heylings JR: Stimulation of alkaline secretion in amphibian-isolated gastric mucosa by 16, 16-dimethyl PGE2 and PGF2. Gastroenterology 76:497–503, 1979 Tao P, Wilson DE: Effects of prostaglandin E2, 16,16-dimethyl prostaglandin E2 and a prostaglandin endoperoxide analog (U-46619) on gastric secretory volume [H+], and mucus synthesis and secretion in the rat. Prostaglandins 28:353–366, 1984 Isenberg JI, Hogan DL, Selling JA, Koss MA: Duodenal bicarbonate secretion in humans: Role of prostaglandins. Dig Dis Sci 31S:1305, 1986 (abstract) Hansky J, Stern AI, Korman MG, Waugh J: Effects of long-term cimetidine on serum gastrin in duodenal ulcer. Dig Dis Sci 24:468–470, 1979 Mohamed R, Holden RJ, Hearns JB, McKibben BM, Buchanan KD, Crean JP: Effects of eight weeks of continuous treatment with oral ranitidine and cimetidine on gastric acid secretion, pepsin secretion and fasting serum gastrin. Gut 24:61–66, 1983 Ippoliti AF, Isenberg JI, Maxwell V, Walsh JH: The effect of 16,16-dimethyl prostaglandin E2 on meal-stimulated gastric acid secretion and serum gastrin in duodenal ulcer patients. Gastroenterology 70:488–491, 1976 Petersen W, Feldman M, Taylor I, Brenner M: The effect of 15(R)-15-methyl prostaglandin E2 on meal-stimulated gastric acid secretion, serum gastrin, and pancreatic polypeptide in duodenal ulcer patients. Dig Dis Sci 24:381–384, 1979 Konturek SJ, Swierczek JS, Kwiecien N, Obtulowicz W, Sito E, Olesky J: Effect of orally administered 15(R)-15-methyl prostaglandin E2 and/or anticholinergic drug on meal-induced gastric acid secretion and serum gastrin level in patients with duodenal ulcers. Scand J Gastroenterol 14:813–819, 1979