Yoshida Kenta, Zhao Ping, Zhang Lei, Abernethy Darrell R, Rekić Dinko, Reynolds Kellie S, Galetin Aleksandra, Huang Shiew-Mei
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, Tennessee 37830.
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
J Pharm Sci. 2017 Sep;106(9):2209-2213. doi: 10.1016/j.xphs.2017.04.045. Epub 2017 Apr 26.
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 provides an overview of currently available in vitro experimental systems and basic in vitro-in vivo extrapolation methodologies for metabolism- and transporter-mediated DDIs.
在药物研发过程中，评估药物相互作用（DDI）风险对于确定 investigational new drugs 的获益-风险概况至关重要。体外实验通常作为评估 investigational new drugs 代谢和转运体介导的 DDI 潜力的重要第一步进行。这些实验的结果通常借助体外-体内外推法进行解释，以确定是否以及如何在临床上评估 DDI，从而为适当的 DDI 管理策略提供依据，包括给药建议、替代疗法或在各种 DDI 情况下及不同患者群体中的禁忌症。本文概述了目前可用的体外实验系统以及用于代谢和转运体介导的 DDI 的基本体外-体内外推方法。
