Antisecretory activity of omeprazole in the conscious gastric fistula cat: comparison with famotidine.

The antisecretory activity of the H+/K+ ATPase inhibitor omeprazole was studied in the conscious gastric fistula cat in comparison with the H2-blocker famotidine. Omeprazole caused a dose-dependent inhibition of the dimaprit-induced acid secretion, being approximately fivefold less potent than famotidine (intravenous ID50S were 0.34 +/- 0.03 and 0.067 +/- 0.015 mumol/kg for omeprazole and famotidine, respectively). Omeprazole caused a non-competitive inhibition of the dose-response curve to dimaprit, whereas famotidine induced a parallel shift to the right without depressing the maximum response. Conversely from famotidine, the antisecretory effect of omeprazole was found to be dependent on the acid secretory state of the stomach, the effect being more evident when the compound was administered at the plateau of acid secretion. The inhibitory effect of omeprazole was very long lasting (25% inhibition was still present 24 h after administration of the drug) whereas that of famotidine was overcome by dimaprit infusion within 3-4 h. The antisecretory effect of omeprazole concerned to the same extent the volume and the acid concentration of the gastric juice, whereas famotidine reduced mainly the volume. When the stimulus was represented by pentagastrin the intravenous ID50 values were 0.57 +/- 0.03 and 0.088 +/- 0.015 mumol/kg for omeprazole and famotidine. respectively. From the above data it may be concluded that the antisecretory profile of omeprazole differed markedly from that of famotidine, independently from the potency and the efficacy of the two drugs.