基于代谢酶和转运体的体外药物相互作用研究概述与案例分析  

Metabolism-and transporter-mediated drug-drug interaction-overview of in vitro study and cases analysis

作　　者：单晓蕾 付淑军 高广花 孙涛[1] 王庆利[1] 余珊珊 SHAN Xiaolei;FU Shujun;GAO Guanghua;SUN Tao;WANG Qingli;YU Shanshan(Center for Drug Evaluation, National Medical Products Administration, Beijing 100022, China)

机构地区：[1]国家药品监督管理局药品审评中心

出　　处：《中国临床药理学与治疗学》2019年第10期1165-1171,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：在药物开发过程中,药物-药物相互作用(DDI)研究是评估新药风险-获益的关键环节。在评价代谢酶或转运体介导的药物相互作用潜力中,通常体外试验是关键的第一步。体外试验分析结果借助于体外-体内模型公式推算,可决定是否需要以及如何开展临床DDI研究,进而为临床DDI风险控制策略提供参考,包括:药物剂量选择、替代治疗、不同DDI情况下以及不同患者群体的用药禁忌等。本文概述了药物研发过程体外DDI研究的关键内容,并通过两个案例阐述了体内和体外DDI研究在药物说明书中相关内容的反映。Evaluation of drug-drug interaction (DDI) risk is vital to establish benefit risk profiles of investigational new drugs during drug development. In vitro experiments are routinely conducted as an important first step to assess metabolism- and transporter-mediated DDI potential of investigational new drugs. Results from these experiments are interpreted, often with the aid of in vitro- in vivo extrapolation methods, to determine whether and how DDI should be evaluated clinically to provide the basis for proper DDI management strategies, including dosing recommendations, alternative therapies, or contraindications under various DDI scenarios and in different patient population. This article summarizes critical elements in the in vitro evaluation of drug interaction potential during drug development and introduces two cases at the end to demonstrate how the in vitro and in vivo study results affect the drug labeling.

关 键 词：药物相互作用 代谢酶 转运体 指导原则 

分 类 号：R969.1[医药卫生—药理学]