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。
Cytochrome 17450 （CYP）-mediated in- hibitory 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 drngs 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 review was to present the fundamentals, predictive strategies, and essential considerations in predicting in rh,o DDI properties from in vitro data.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2009年第8期841-848,共8页
Chinese Journal of Clinical Pharmacology and Therapeutics
