Abstract
Misoprostol, a synthetic analog of prostaglandin E1, inhibits gastric acid production and is cytoprotective at doses well tolerated by patients in preliminary trials. This multicenter double-blind study was performed in out-patients with endoscopically demonstrated duodenal ulcers, to compare the efficacy in ulcer healing and the safety of two dosages of misoprostol and placebo. Up to six antacid tablets daily were permitted for pain. 308 patients enrolled and were randomized to three treatment groups: placebo, misoprostol 50 μg and misoprostol 200 μg. After two weeks of treatment, the three groups had similar percentages of patients with complete ulcer healing. However, after four weeks, 76.6% of patients taking misoprostol 200 μg q.i.d. had complete healing, compared with 42.6% on misoprostol 50 μg q.i.d. and 51% on placebo (P<0.001, 200 μg versus placebo). Patients taking misoprostol 200 μg used less antacid than the others. Diarrhea, mild and self-limiting, was present in 13% of the 200 μg group versus 5% on placebo. We conclude that misoprostol 200 μg q.i.d. is effective, safe and well tolerated in the treatment of duodenal ulcers.
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Main IHM, Whittle BJR: The effects of E and A prostaglandins on gastric mucosal blood flow and acid secretion in the rat. Br J Pharmacol 49:428–436, 1973
Whittle BJR: Actions of prostaglandins on gastric mucosal blood flow.In Gastrointestinal Mucosal Blood Flow, LP Fielding (ed). Edinburgh, Churchill Livingstone, 1980, pp 180–191
Bolton P, Palmer D, Cohen MM: Stimulation of mucus and non-parietal cell secretion by the E2 prostaglandins. Am J Dig Dis 23:359–364, 1978
Way L, Durbin RP: Inhibition of gastric acid secretionin vitro by prostaglandin E1. Nature 221:874–875, 1969
Wilson DE, Phillips C, Levine RA: Inhibition of gastric secretion in man by prostaglandin A1. Gastroenterology 61:201–206, 1971
Karim SMM, Fung WP: Effects of some naturally occurring prostaglandins and synthetic analogs on gastric secretion and ulcer healing in man.In Advances in Prostaglandin and Thromboxane Research, B Samuelson, R Paoletti (eds). New York. Raven Press, 1976, pp 529–538
Cheung LY: Topical effects of 16, 16-dimethyl prostaglandin E2 on gastric blood flow in dogs. Am J Physiol 238:G514–519, 1980
Main IHM, Whittle BJR: Potency and selectivity of methyl analogues of prostaglandin E2 on rat gastrointestinal function. Br J Pharmacol 54:309–317, 1975
Robert A: Antisecretory, anti-ulcer, cytoprotective and diarrheogenic properties of prostaglandins.In Advances in Prostaglandin and Thromboxane Research, vol. 2, B Samuelson, JR Vane (eds). New York, Raven Press, 1976, pp 507–520
Robert A: The inhibitory effects of prostaglandins on gastric secretion: their possible role in the treatment of gastric hypersecretion and peptic ulceration.In Progress in Gastroenterology vol III, 123, GB Jerzy Glass (ed). New York, Grune and Stratton, 1977, pp 777–801
Shea-Donohue T, Nonpleggi D, Myers L, Dubois A: A comparison of the effects of prostacyclin and the 15(S), 15-methyl analogues of PGE2 and PGF2α on gastric parietal and non-parietal secretion. Dig Dis Sci 27:17–22, 1982
Wilson DE, Winnan J, Quertermus J, Tao P: Effects of an orally administered prostaglandin analogue: 16, 16-dimethyl prostaglandin E2 on human gastric secretion. Gastroenterology 69:607–611, 1975
Vantrappen G, Janssens SJ, Popiela T, Kulig J, Tytgat GNJ, Huibregste K, Lambert R, Pauchard JP, Robert A: Effect of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on the healing of duodenal ulcer. Gastroenterology 83:357–363, 1982
Dajani EZ, Driskill DR, Bianchi RG, Collins PW, Pappo R: SC-29333: A potent inhibitor of canine gastric secretion. Dig Dis Sci 12:1049–1057, 1976
Akdamar K, Agrawal N, Ertma A: Inhibition of nocturnal gastric secretion in normal human volunteers by misoprostol: a synthetic prostaglandin E1 methyl ester analog. Am J Gastroenterol 77:902–904, 1982
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 a prostaglandin E1 derivative, SC-29333, and aspirin on gastric ionic fluxes and potential difference in dogs. J Pharmacol Exp Ther 210:283–288, 1979
Larsen KR, Jensen NS, David EK, Jensen JC, Moody FG: The cytoprotective effects of (±) 15-deoxy-16-hydroxy-16-methyl PGE1 methyl ester (SC-29333) vs. 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
Elashoff JD: Statistical considerations in drug trials of peptic ulcer. J Clin Gastroenterol 3(Suppl):135–140, 1981
Conover WJ: Practical Non-parametric Statistics, 2nd ed. New York, John Wiley & Sons, 1980, pp 130–133
Hollander M, Wolfe DA: Non-parametric Statistical Methods, New York, John Wiley & Sons, 1973, p 125
Fleiss JL: Statistical Methods for Rates and Proportions. New York, John Wiley & Son, 1973, pp 77–80
Fogarty International Commission, U.S.P.H.S. NIH Publication No. 79-313, 1979.
Langman MJS: Antacids for duodenal ulcer? Br Med J 285:1520–1521, 1982
Lam SK, Lam KC, Lai CL, Yeung CK, Yam LYC, Wong WS: Treatment of duodenal ulcer with antacid and sulpiride. Gastroenterology 76:315–322, 1979
Binder HJ, Cocco A, Crossley RJ, Finkelstein W, Font R, Friedman G, Groarke J, Hughes W, Johnson AF, McGuigan JE, Summers R, Vlahcevic R, Wilson EC, Winship DH: Cimetidine in the treatment of duodenal ulcer: A multicenter double blind study. Gastroenterology 74:380–387, 1978
Peterson WL, Sturdevant RAL, Frankl HD, Richardson CT, Isenberg JI, Elashoff JD, Sones JQ, Gross RA, McCallum RW, Fordtran JS: Healing of duodenal ulcer with an antacid regimen. N Engl J Med 297:341–345, 1977
McHardy GG: A multicenter, double-blind trial of sucralfate and placebo in duodenal ulcer. J Clin Gastroenterol 3(Suppl 2):147–152, 1981
Korman MG, Hansky J, Merrett AC, Schmidt GT: Ranitidine in duodenal ulcer: incidence of healing and the effect of smoking. Dig Dis Sci 27:712–715, 1982
Carter DC, Karim SMM, Bhana D, Ganesan PA: Inhibition of human gastric secretion by prostaglandins. Br J Surg 60:838, 1973
Wilson DE, Quertermus J, Raiser M, Curran J, Robert A: Inhibition of stimulated gastric secretion by an orally administered prostaglandin capsule: a study in normal men. Ann Intern Med 84:688–691, 1976
Chen FWK, Teck HS, Karim SMM: The effect of 15(R)-15-methyl prostaglandin E2 on gastric acid secretion in duodenal ulcer patients. Prostaglandins 13:115–124, 1977
Major JS, Scholes P: The localization of a histamine H2-receptor cyclase system in canine parietal cells and its inhibition by prostaglandins. Agents Actions 8:324–331, 1978
Wollin AW, Soll AH, Samloff IM: Actions of histamine, secretin, and prostaglandin E2 on cyclic AMP production by isolated canine fundic mucosal cells. Am J Physiol 237:E437–443, 1979
Soll AH: Specific inhibition by prostaglandins E2 and I2 of histamine-stimulated14C-aminopyrine accumulation and cyclic AMP generation by isolated canine parietal cells. J Clin Invest 65:1222–1229, 1980
Longstreth GF, Malagelada JR: Cimetidine suppression of nocturnal gastric secretion in active duodenal ulcer. N Engl J Med 294:801–804, 1976
Pounder RE, Williams JG, Russell RCG, Milton-Thompson GS, Misiewicz JJ: Inhibition of food-stimulated gastric acid secretion by cimetidine. Gut 17:161–168, 1976
Richardson CT, Walsh JH, Hicks MI: The effect of cimetidine, a new histamine H2-receptor antagonist, on mealstimulated acid secretion, serum gastrin, and gastric emptying in patients with duodenal ulcer. Gastroenterology 71:19–23, 1976
Cohen MM: Mucosal cytoprotection by prostaglandin E2. Lancet 2:1253–1254, 1978
Johansson C, Kollberg B, Nordeman R, Bergstrom S: Mucosal protection by prostaglandin E2. Lancet 1:317, 1979
Johansson C, Kollberg B, Nordeman R, Samuelson K, Bergstrom S: Protective effect of prostaglandin E2 in the gastrointestinal tract during indomethacin treatment of rheumatic diseases. Gastroenterology 78:479–493, 1980
Yik JY, Dreidger AA, Watson WC: Prostaglandin E2 tablets prevent aspirin-induced blood loss in man. Gastroenterology 78:1296, 1980
Ruppin H, Person B, Robert A, Domschke W: Gastric cytoprotection by prostaglandins (PG): possible mediation by mucus secretion. Physiologist 22:110, 1979
Ruppin H, Person B, Domschke W, Robert A: Zytoprotective Wirkungen von Prostaglandin E2 auf die Magenschleimhaut beim Menschen. Dtsch Med Wochenschr 104:1457–1458, 1979
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
Bardhan KD, Saul DM, Edwards JL, Smith PM, Fettes M, Forest J, Heading RC, Logan RFA, Dronfield MW, Langman MJ, Larkworthy W, Haggie SJ, Wyllie JH, Corbett C, Duthie HL, Fussey IV, Holdsworth CD, Balmforth GV, Maruyama T: Comparison of two doses of cimetidine and placebo in the treatment of duodenal ulcer: a multicenter trial. Gut 20:68–74, 1979
Korman MG, Shaw RG, Hansky J, Schmidt GT, Stern AI: Influence of smoking on healing rate of duodenal ulcer in response to cimetidine or high-dose antacid. Gastroenterology 80:1451–1453, 1981
Bianchi Porro G, Prada A, Petrillo M, Lazzaroni M: Women and duodenal ulcer. Br Med J 283:235, 1981
Konturek SJ, Brzozowski T, Prastucki I, Radecki T, Dembinski A, Dembinska-Kiec A: Role of locally generated prostaglandins in adaptive gastric cytoprotection. Dig Dis Sci 27:967–971, 1982
Halter F, Reinhart WH, Koelz HR, Meyrat P, Lentze MJ, Muller O: 16, 16-dimethyl prostaglandin E2 stimulates growth and maturation of rat gastric and small intestinal mucosa. Scand J Gastroenterol 19(Suppl 92):178–183, 1984
Morson BC, Sobin LH, Grundmann E, Johansen A, Nagayo T, Serck-Hanssen A: Precancerous conditions and epithelial dysplasia in the stomach. J Clin Pathol 33:711–721, 1980
Grundmann E, Schlake W: Histology of possible precancerous stages in the stomach.In Gastric Cancer, C Herford, P Schlag (eds). New York, Springer-Verlag, 1979, pp 72–82
Kimberg DV, Field M, Johnson J, Hendersen A, Gershon E: Stimulation of intestinal mucosal adenocyclase by cholera enterotoxin and prostaglandins. J Clin Invest 50:1218–1230, 1971
Kimberg DV, Field M, Gershon E, Hendersen A: Effects of prostaglandins and cholera enterotoxin on intestinal mucosal cyclic AMP accumulation. J Clin Invest 53:941–949, 1974
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Brand, D.L., Roufall, W.M., Thomson, A.B.R. et al. Misoprostol, a synthetic PGE1 analog, in the treatment of duodenal ulcers. Digest Dis Sci 30 (Suppl 11), 147S–158S (1985). https://doi.org/10.1007/BF01309402
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DOI: https://doi.org/10.1007/BF01309402