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 mumol/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 histamine-stimulated acid secretion was found to be 1.2 mumol/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 approximately 70% whereas the oral bioavailability was only approximately 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 mumol/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 approximately 13 h.
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002927:Cimetidine; D004285:Dogs; D004386:Duodenum; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D009853:Omeprazole; D051381:Rats; D011919:Rats, Inbred Strains; D014628:Vagotomy
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D002927:Cimetidine; D009853:Omeprazole; C028887:picoprazole