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灌注大鼠肝脏中水杨酸肝代谢的评估

Evaluation of hepatic metabolism of salicylic acid in perfused rat liver.

作者信息

Shetty B V, Badr M, Melethil S

机构信息

University of Missouri-Kansas City, School of Pharmacy 64108-2792.

出版信息

J Pharm Sci. 1994 Apr;83(4):607-8. doi: 10.1002/jps.2600830433.

Abstract

Hepatic metabolism of salicylic acid was studied using a single-pass liver perfusion technique. Livers obtained from male, Sprague-Dawley rats (200-300 g) were perfused with Krebs-Henseleit bicarbonate buffer containing the drug (50-100 micrograms/mL) and glycine (0.5 or 5 mM) or glucose (5.5 mM) or bovine serum albumin (0.33%). Effluent samples over a 30-50 min interval were analyzed for salicylic acid and its metabolites (gentisic acid, salicyluric acid, and salicyl acyl and salicyl phenolic glucuronides). Effluent concentrations of salicylic acid did not differ from those in the perfusate, indicating that the liver is not a site for the metabolism of this drug. Hepatic uptake studies are needed to confirm this finding.

摘要

采用单通道肝脏灌注技术研究了水杨酸的肝脏代谢情况。从雄性Sprague-Dawley大鼠(200 - 300克)获取的肝脏,用含有药物(50 - 100微克/毫升)以及甘氨酸(0.5或5毫摩尔)或葡萄糖(5.5毫摩尔)或牛血清白蛋白(0.33%)的Krebs-Henseleit碳酸氢盐缓冲液进行灌注。对30 - 50分钟时间段内的流出液样本进行水杨酸及其代谢产物(龙胆酸、水杨尿酸以及水杨酰和水杨酚葡萄糖醛酸苷)分析。流出液中水杨酸的浓度与灌注液中的浓度没有差异,表明肝脏不是该药物的代谢部位。需要进行肝脏摄取研究以证实这一发现。

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