Effect of Trimoprostil on Gastric Secretion Takeshi KAWAMURA * Hiroko EBINA * Fumiaki KOIZUMI * and Akira ISHIMORI * *Department of Clinical and Labor
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1 Effect of Trimoprostil on Gastric Secretion Takeshi KAWAMURA * Hiroko EBINA * Fumiaki KOIZUMI * and Akira ISHIMORI * *Department of Clinical and Laboratory Medicine University School of Medicine, Tohoku The effects of trimoprostil, an analogue of PGE2, on gastric secretion was studied in 'healthy volunteers in comparison with those of cimetidine. Graded doses of 50, 250, 500, however. On the other hand, cimetidine inhibited gastrin-stimulated gastric acid and pepsin secretion remarkably. Some difference was also recognized between trimoprostil and cimetidine concerning the mechanism of inhibitory effect. Serum concentration of trimoprostil was measured at 60 min. after oral administration varied dose-dependently and dose-related anti-secretory effects were also found. Serum gastrin and pepsinogen 1 were not affected either by trimoprostil or cimetidine. These results indicate that Key words : trimoprostil, prostaglandin E2, gastric secretion, pepsinogen 1, gastrin
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3 Tab. 1 Serum Concentration of Trimoprostil After a Single Oral Administration to Healthy Subjects. in Fasting State
4 350 Tab. 2 The Inhibitory Effects of Trimoprostil on Basal and AOC-Tetragastrin Stimulated Gastric Secretion
5 Fig. 2 Alteration of ph after oral dose of trimoprostil. Date were shown as mean of 8 Fig. 3 Alteration of acid concentration after oral dose of trimoprostil. Data were shown as mean of 8 subjects.
6 Fig. 4 Alteration of gastric volume after oral dose of trimoprostil. Data were shown as mean of 8 subjects. Fig. 5 Alteration of gastric acid secretion after oral dose of trimoprostil. Data were shown as mean of 8 subjects.
7 Tab. 3 The Inhibitory Effects of Trimoprostil on Cumulative Acid Output Fig. 6 Cumulative acid output after oral dose of trimoprostil. Data were shown as mean of 8 subjects.
8 Fig. 7 Alteration of pepsin concentration after oral dose of trimoprostil. Data were shown as mean of 8 subjects. Fig. 8 Alteration of gastric pepsin secretion after oral dose of trimoprostil. Data were shown as mean of 8 subjects.
9 Tab. 4 The Inhibitory Effects of Trimoprostil on Cumulative Pepsin Output Fig. 9 Cumulative pepsin output after oral dose of trimoprostil. Data were shown as mean of 8 subjects.
10 Tab. 5 Serum Gastrin Before and After Oral Dose of Trimoprostil Tab. 6 Serum Pepsinogen 1 Before and After Oral Dose of Trimoprostil
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13 Fig. 10 Cumurative acid output (a) and pepsin output (b) after oral dose of cimetidine in 6 subjects. (b)
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15 histamine-stimulated gastric mucosal blood flow. Digestive Disease & Sciences. 25 : (1980). 4) Robert, A., Nezamis, J. E., Lancaster, C. et al. : Cytoprotection by prostaglandines in rats. 1) Robert, A., Nezamis, J. E. and Phellips, J. P.: Inhibition of gastric secretion by prostaglandin. Amer. J. Digest. Dis., 12 : (1967). 2) Domschke, W., Domschke, S., Horing, D. et al. : Prostaglandin stimulated gastric mucus secretion in man. Acta Hepato-Gastroenterol., 25 : (1978). 3) Miller, T. M., Hengan, J: M. and Robert, A.: Effect of 16, 16-dimethyl PG E2 on resting and Gastroenterology, 77 : (1979). 5) Ippoliti, A. F., Isenberg, J. I., Maxwell, V. et al.: The effcet of 16, 16-dimethyl prostaglandin E2 on meal-stimulated gastric acid secre- tion and serum gastrin in duodenal ulcer patien,ts. Gastroenterology, 70 : (1976). 6) Rask-Madsen, J. and Bukhave, K. : Prostaglandins and chronic diarrhea. Clinical aspects. Scand. J. Gastroenterol., 14, Supp. 53 : (1979). 11) Ohno, T., Yajima, T., Urano, T. et al.: Interaction of prostaglandin E2 and bradykinin in the induction of afferent splenchnic nerve discharges in cats. Japan J. Pharmacol., 34 : (1984).
16 16) Konturek, S. J., Kwiecien, N., Obtulowicz, W. et al.: Comparison of prostaglandin E2 and ranitidine in prevention of gastric bleeding by asoirin in man. Gut. 24 : (1983). 18) Rotter, J. I., Sones, J. Q., Samloff, I. M. et al.: Duodenal ulcer disease associated with elevated serum pepsinogen-i. An inherited autosomal dominant disorder. N. Engl. J. Med., 300 :63-65 (1979). 20) Spence, R. W., Creak, D. R. and Celestin, L. R. : Influence of a meal on the absorption of cimetidine. Digestion, 14 : (1976). 21) Miller, T. A., Kraemer, B. B., Henagan, J. M. et al.: Topical 16, 16-dimethyl-prostaglandin E2. Dig. Dis, Sci., 28 : , (1983). 22) Inatomi. N., Sato. N., Sato. H. et al.: Indomethacin-induced changes in canine gastric mucosal haemodynamics and haemoglobin oxygenation, and the effects of topical anti-ulcer agents. J. Gastroent. Hepatol., 1 : (1986).
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