Okabe S, Shimosako K, Harada H
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Jpn J Pharmacol. 1995 Oct;69(2):91-100. doi: 10.1254/jjp.69.91.
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.
雷米拉唑是一种酸泵抑制剂，经全身或局部给药时，能显著降低大鼠基础胃酸分泌量和刺激胃酸分泌量。我们的目的是研究雷米拉唑对清醒犬胃酸分泌的抑酸作用。通过静脉输注组胺刺激迷走神经切断的海登海因小胃犬的胃酸分泌。在输注组胺之前或之后，将雷米拉唑或奥美拉唑（作为参比药物）静脉注射或局部注入小胃。分别静脉推注雷米拉唑和奥美拉唑，均能显著且呈剂量依赖性地抑制刺激胃酸分泌超过26小时。局部应用雷米拉唑（而非奥美拉唑）15至30分钟能显著抑制胃酸分泌。应用30分钟后观察到的局部抑酸作用持续时间约为8至10小时。雷米拉唑的酸降解产物应用于小胃时无作用。局部应用1小时后雷米拉唑的血药浓度很低。这些结果表明，雷米拉唑可通过静脉和局部途径抑制犬壁细胞的分泌功能。局部应用雷米拉唑是否通过抑制酸泵产生抑酸作用尚不清楚。
