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

doi:10.12092/j.issn.1009-2501.2019.10.013

Abstract

Abstract:

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.

Key words: drug-drug interaction, metabolizing enzymes, membrane transporters, guidance

CLC Number:

R969.1

SHAN Xiaolei, FU Shujun, GAO Guanghua, SUN Tao, WANG Qingli, YU Shanshan. Metabolism- and transporter-mediated drug-drug interaction-overview of in vitro study and cases analysis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(10): 1165-1171.

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