Antisecretory effect of leminoprazole on histamine-stimulated gastric acid secretion in dogs: potent local effect.
Leminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated gastric acid secretion in rats when administered via the systemic or local route. Our aim here was to characterize the antisecretory effect of leminoprazole on gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a vagally denervated Heidenhain pouch was stimulated by intravenous histamine infusion. Leminoprazole or omeprazole (as a reference drug) was administered either intravenously or locally into the pouch before or after histamine infusion. A bolus intravenous administration of leminoprazole and omeprazole, respectively, significantly and dose-relatedly inhibited the stimulated gastric acid secretion for > 26 hr. Local application of leminoprazole, but not omeprazole, significantly inhibited the acid secretion when applied for 15 to 30 min. The duration of the local antisecretory effect observed after 30 min application was around 8-10 hr. The acid-degraded products of leminoprazole had no effect when applied to the pouch. The blood concentration of leminoprazole was very low at 1 hr after local application. These results indicate that leminoprazole suppresses the secretory function of the parietal cells of dogs, via both the intravenous and local routes. It remains unknown whether or not locally applied leminoprazole produced the acid inhibition by inhibiting the acid pump.
Okabe
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Shimosako
K
K
Harada
H
H
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; C089751:leminoprazole; D006632:Histamine; D009853:Omeprazole