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The inhibitory action of leminoprazole on the activity of rat gastric mucosal H+,K(+)-ATPase was investigated in vitro and ex vivo. Leminoprazole and omeprazole concentration-dependently inhibited the H+,K(+)-ATPase activity, and their IC50 values were 31 microM and 24 microM, respectively, at pH7.4. Leminoprazole dose-dependently inhibited the H+,K(+)-ATPase activity at 3 and 6 hr after the administration at 10-100 mg/kg, p.o. Leminoprazole (60 mg/kg, p.o.) inhibited the H+,K(+)-ATPase activity persistently, and the duration of its inhibitory action was much longer than that of omeprazole (30 mg/kg, p.o.). In pylorus-ligated rats, good correlations between the respective inhibitory rates against gastric acid output and H+,K(+)-ATPase activity was found after the administration of leminoprazole. These results suggest that leminoprazole inhibits the gastric acid secretion by its ability to inhibit the H+,K(+)-ATPase activity in rats; its inhibitory activity was comparable to that of omeprazole. In addition, leminoprazole (100 mg/kg) inhibited the H+,K(+)-ATPase activity even when administered intragastrically after pylorus-ligation, suggesting that this drug can inhibit H+,K(+)-ATPase activity directly from the gastric lumen. Moreover, leminoprazole (100 mg/kg, p.o.) when administered repeatedly for 2 or 4 weeks inhibited the H+,K(+)-ATPase activity to the same degree as the single administration.

Effect of a new antiulcer drug, leminoprazole, on the gastric mucosal H+, K+-ATPase activity in rats.