长期给予环孢素A对大鼠苯妥英药代动力学参数的影响。

The effect of chronic administration of cyclosporin A on phenytoin pharmacokinetic parameters in the rat.

作者信息

Wasfi I A, Tanira M O

机构信息

Desert and Marine Environment Research Center, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain.

出版信息

Life Sci. 1993;52(2):199-204. doi: 10.1016/0024-3205(93)90140-x.

DOI:10.1016/0024-3205(93)90140-x

PMID:8355560

Abstract

The potential for a drug interaction between cyclosporin A and phenytoin was investigated in rats. Rats were treated daily for 14 days with cyclosporin A (50 mg/Kg, s.c.) and on the day of the experiment phenytoin (10 mg/Kg) was administered intravenously. The mean residence time, the elimination half-life and the volume of distribution at steady state were significantly higher in the cyclosporin A-treated group than in the control group. However, total body clearance was similar in both groups. Plasma levels of urea, aspartate aminotransferase (AST) and glucose were significantly higher in the cyclosporin A-treated group than the control group. It was concluded that the observed changes could have been, at least in part, due to an inhibitory effect of cyclosporin A on liver drug metabolizing enzymes and/or liver and kidney damage.

摘要

在大鼠中研究了环孢素A与苯妥英之间药物相互作用的可能性。大鼠连续14天每天皮下注射环孢素A（50mg/Kg），在实验当天静脉注射苯妥英（10mg/Kg）。环孢素A治疗组的平均驻留时间、消除半衰期和稳态分布容积显著高于对照组。然而，两组的总体清除率相似。环孢素A治疗组的血浆尿素、天冬氨酸转氨酶（AST）和葡萄糖水平显著高于对照组。得出的结论是，观察到的变化可能至少部分归因于环孢素A对肝脏药物代谢酶的抑制作用和/或肝脏及肾脏损伤。