CYP介导的抑制性药物相互作用的体外定量预测

摘要/Abstract

摘要： 细胞色素 P450 酶(cytochrome P450, CYP)介导的抑制性药物相互作用在新药研发和临床实践中受到了极大的关注。不少药物在上市后因CYP 抑制性药物相互作用而产生严重的不良反应,导致此类药物受到严格的用药限制或被迫退出市场。这不仅给病人带来危害, 也为制药公司造成巨大的经济损失。体外试验以其便利性和高通量性 ,被广泛应用于 CYP 介导的药物相互作用的研究。然而, 体外数据并不能直接反映体内情况,研究者需要通过数据处理将之转变为可直观评价的数据来对体内 CYP 抑制性药物相互作用的可能性及程度进行预测。目前这一研究领域发展十分迅速 ,本综述对这一研究领域的相关基础知识、基本预测方法及相关重要影响因素进行详细深入的介绍。

关键词: 细胞色素 P450 酶, 药物相互作用, 可逆性抑制, 不可逆性抑制, 机理性抑制

Abstract: Cytochrome P450 (CYP)-mediated inhibitory drug and drug interaction(DDI)potential must be well evaluated during the course of drug discovery and development .It is not uncommon that drug inhibition of CYPs may lead to severe prescribing restrictions, or withdrawal of drugs from market .Not only may this kind of DDI jeopardize patients' safety , but also cause huge financial losses for drugmakers. In vitro strategy , due to its simplicity and high throughput possibility , has been routinely used to evaluate the potential of CYP-mediated DDI .However , in vitro data only provide indirect information. For this reason, in vitro inhibition data are frequently used to predict in vivo CYP-mediated inhibitory DDI potential .Further, such predicted data can be taken into consideration in designing clinical trials.In recent years, this field has undergone rapid development .The purpose of this re-view was to present the fundamentals, predictive strategies, and essential considerations in predicting in vivo DDI properties from in vitro data.

Key words: cytochrome P450, drug-drug interaction, reversible inhibition, irreversible inhibition, mech-anism-based inhibition

中图分类号:

R969

郭建军, 赵华, 王晶晶. CYP介导的抑制性药物相互作用的体外定量预测[J]. 中国临床药理学与治疗学, 2009, 14(8): 841-848.

GUO Jian-jun, ZHAO Hua, WANG Jing-jing. In vitro prediction of CYP-mediated inhibitory drug and drug interaction[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(8): 841-848.

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