Inhibition of gastric acid secretion by omeprazole in the dog and rat

The gastric antisecretory properties of omeprazole, a new potent substituted benzimidazole, have been evaluated in dogs and rats. Omeprazole was compared with another benzimidazole, picoprazole (H 149/94), and with the histamine H2-receptor antagonist cimetidine. The intravenous or intraduodenal administration of omeprazole in the gastric fistula dog inhibited histamine- and pentagastrin-stimulated acid secretion. The intravenous and intraduodenal, ED50 values for inhibition of histamine-stimulated secretion were 0.35 and 0.26 μmol/kg, respectively. Omeprazole was found to be approximately 5–10 times more potent than both picoprazole and cimetidine. After oral omeprazole administration in the Heidenhain pouch dog, the ED50 on histaminestimulated acid secretion was found to be 1.2 μmol/kg, which corresponded to a potency 2 and 3.5 times greater than that of cimetidine and picoprazole, respectively. Measurement of the plasma concentration of unchanged omeprazole revealed an intraduodenal bioavailability of ∼70% whereas the oral bioavailability was only ∼15%. This variation is probably a result of partial degradation of omeprazole in the acid gastric juice. Single intraduodenal doses of omeprazole had a long-lasting inhibitory effect on histamine-stimulated acid secretion in the dog. After a dose of omeprazole, which produced total inhibition initially, the antisecretory effect was detectable for 3–4 days. Omeprazole inhibited basal and stimulated acid secretion in the rat. The intravenous ED50 was calculated to be 1.5 μmol/kg, whereas the oral potency was about 10 times lower. The effect in the rat was also of long duration. After a dose giving maximal inhibition, control acid secretion was restored after ∼13 h.