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J Pharm Sci. 2017 Sep;106(9):2209-2213. doi: 10.1016/j.xphs.2017.04.045. Epub 2017 Apr 26.

In Vitro-In Vivo Extrapolation of Metabolism- and Transporter-Mediated Drug-Drug Interactions-Overview of Basic Prediction Methods.

Author information

1
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.
2
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
3
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; Centre for Applied Pharmaceutical Research, School of Health Sciences, University of Manchester, Manchester, M13 9PL, UK.
4
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993. Electronic address: ShiewMei.Huang@fda.hhs.gov.

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 provides an overview of currently available in vitro experimental systems and basic in vitro-in vivo extrapolation methodologies for metabolism- and transporter-mediated DDIs.

KEYWORDS:

cytochrome P450s; drug interaction; guidance/guideline; membrane transport/transporters; regulatory

PMID:
28456729
DOI:
10.1016/j.xphs.2017.04.045
[Indexed for MEDLINE]

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