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新型H+/K+-ATP酶抑制剂泮托拉唑对大鼠十二指肠溃疡形成和愈合反应的影响:与奥美拉唑和兰索拉唑的比较研究

Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats: a comparative study with omeprazole and lansoprazole.

作者信息

Takeuchi K, Konaka A, Nishijima M, Kato S, Yasuhiro T

机构信息

Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.

出版信息

J Gastroenterol Hepatol. 1999 Mar;14(3):251-7. doi: 10.1046/j.1440-1746.1999.01843.x.

DOI:10.1046/j.1440-1746.1999.01843.x
PMID:10197495
Abstract

BACKGROUND

Pantoprazole, 2-[(2-pyridylmethyl) sulphinyl] benzimidazole, is a new substituted benzimidazole that inhibits the parietal cell H+/K+-ATPase.

METHODS

In the present study, the anti-secretory and anti-ulcer activities of pantoprazole were compared with those of omeprazole and lansoprazole in rats.

RESULTS

Pantoprazole (0.3-3 mg/kg, p.o.) as well as omeprazole (1-10 mg/kg, p.o.) and lansoprazole (1-10 mg/kg, p.o.) dose-dependently decreased both basal acid secretion in pylorus-ligated rats and the stimulated acid secretion induced by mepirizole in acute fistula rats, and the effects of pantoprazole were more potent than those of omeprazole and lansoprazole, the ED50 values for the stimulated acid secretion being 0.8, 2.0 and 1.2 mg/kg, respectively. Neither of these drugs had any effect on duodenal HCO3- secretion. These pump inhibitors prevented the development of duodenal lesions in response to mepirizole in a dose-related manner, the ED50 values for pantoprazole, omeprazole and lansoprazole being 0.4, 2.0 and 1.3 mg/kg, respectively. Likewise, pantoprazole showed the healing promoting action on chronic duodenal ulcers induced by acetic acid, and this effect was also more potent when compared to omeprazole or lansoprazole.

CONCLUSIONS

We conclude that pantoprazole exhibited both anti-ulcer and healing promoting effects on duodenal ulcers in rats, and the effects may be attributable to its potent anti-secretory action. Other pump inhibitors such as omeprazole and lansoprazole were almost equally effective as pantoprazole, yet this drug was most potent on the basis of ED50 values.

摘要

背景

泮托拉唑,即2 - [(2 - 吡啶基甲基)亚磺酰基]苯并咪唑,是一种新型取代苯并咪唑,可抑制壁细胞H⁺/K⁺ - ATP酶。

方法

在本研究中,将泮托拉唑与奥美拉唑和兰索拉唑在大鼠体内的抗分泌及抗溃疡活性进行了比较。

结果

泮托拉唑(0.3 - 3毫克/千克,口服)以及奥美拉唑(1 - 10毫克/千克,口服)和兰索拉唑(1 - 10毫克/千克,口服)均剂量依赖性地降低幽门结扎大鼠的基础胃酸分泌以及急性瘘管大鼠中由甲哌噻吨诱导的刺激胃酸分泌,且泮托拉唑的作用比奥美拉唑和兰索拉唑更强,刺激胃酸分泌的半数有效剂量(ED50)值分别为0.8毫克/千克、2.0毫克/千克和1.2毫克/千克。这些药物对十二指肠HCO₃⁻分泌均无影响。这些质子泵抑制剂以剂量相关的方式预防了由甲哌噻吨引起的十二指肠损伤,泮托拉唑、奥美拉唑和兰索拉唑的ED50值分别为0.4毫克/千克、2.0毫克/千克和1.3毫克/千克。同样,泮托拉唑对乙酸诱导的慢性十二指肠溃疡具有促愈合作用,与奥美拉唑或兰索拉唑相比,这种作用也更强。

结论

我们得出结论,泮托拉唑对大鼠十二指肠溃疡具有抗溃疡和促愈合作用,其作用可能归因于其强大的抗分泌作用。其他质子泵抑制剂如奥美拉唑和兰索拉唑与泮托拉唑几乎同样有效,但基于ED50值,泮托拉唑最为强效。

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