机理性灭活体外细胞色素P450 及其对体内药物相互作用定量预测的研究进展

摘要/Abstract

摘要： 近10年来, 以体外细胞色素P450 抑制数据预测潜在临床药物相互作用的方法得到极大发展。药物相互作用(drug-drug interaction) 研究一直是临床实践和新药开发中的重要环节。本文对近年来引起广泛重视的机理性灭活作用(mechanismbased inactivation) 进行总结分析, 综合传统和经简化的鉴定机理性灭活作用方法, 并介绍预测体内由机理性灭活引起药物相互作用的模型和影响参数。

关键词: 药物相互作用, 不可逆性抑制, 机理性灭活, 细胞色素P450, 体外-体外预测

Abstract: In the last decade, the approaches for the invitro inhibition assessment of the potentials of drug-drug interaction in vivo have received process. DDIs remain an important issue in clinical practice and the development of new drugs.Mechanism-based inactivation is gaining more attention among in vitro study. This review would describe methods in identifying mechanism-based inactivation, and introduce predictive models and parameters in the field.

Key words: drug-drug interaction, irreversible inhibition, mechanism-based inactivation, cytochrome P450, in vitro-in vivo extrapolation

中图分类号:

R968

曹杉, 周宏灏. 机理性灭活体外细胞色素P450 及其对体内药物相互作用定量预测的研究进展[J]. 中国临床药理学与治疗学, 2008, 13(3): 241-248.

CAO Shan, ZHOU Hong-hao. Advances in predicting of drug-drug interaction in vivo by using cytochrome P450 mechanism-based inhibition data in vitro[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(3): 241-248.

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