The AAPS Journal

, Volume 15, Issue 3, pp 629–645

Drug–Drug Interaction Studies: Regulatory Guidance and An Industry Perspective

  • Thomayant Prueksaritanont
  • Xiaoyan Chu
  • Christopher Gibson
  • Donghui Cui
  • Ka Lai Yee
  • Jeanine Ballard
  • Tamara Cabalu
  • Jerome Hochman
Commentary

DOI: 10.1208/s12248-013-9470-x

Cite this article as:
Prueksaritanont, T., Chu, X., Gibson, C. et al. AAPS J (2013) 15: 629. doi:10.1208/s12248-013-9470-x

Abstract

Recently, the US Food and Drug Administration and European Medicines Agency have issued new guidance for industry on drug interaction studies, which outline comprehensive recommendations on a broad range of in vitro and in vivo studies to evaluate drug–drug interaction (DDI) potential. This paper aims to provide an overview of these new recommendations and an in-depth scientifically based perspective on issues surrounding some of the recommended approaches in emerging areas, particularly, transporters and complex DDIs. We present a number of theoretical considerations and several case examples to demonstrate complexities in applying (1) the proposed transporter decision trees and associated criteria for studying a broad spectrum of transporters to derive actionable information and (2) the recommended model-based approaches at an early stage of drug development to prospectively predict DDIs involving time-dependent inhibition and mixed inhibition/induction of drug metabolizing enzymes. We hope to convey the need for conducting DDI studies on a case-by-case basis using a holistic scientifically based interrogative approach and to communicate the need for additional research to fill in knowledge gaps in these areas where the science is rapidly evolving to better ensure the safety and efficacy of new therapeutic agents.

Key words

drug–drug interaction studiesindustry perspectiveregulatory guidance

Supplementary material

12248_2013_9470_MOESM1_ESM.doc (187 kb)
ESM 1DOC 187 kb

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Thomayant Prueksaritanont
    • 1
  • Xiaoyan Chu
    • 2
  • Christopher Gibson
    • 1
  • Donghui Cui
    • 1
  • Ka Lai Yee
    • 1
  • Jeanine Ballard
    • 1
  • Tamara Cabalu
    • 1
  • Jerome Hochman
    • 1
  1. 1.Department of Pharmacokinetics, Pharmacodynamics, and Drug MetabolismMerck Sharp and Dohme Corp.West PointUSA
  2. 2.Department of Pharmacokinetics, Pharmacodynamics, and Drug MetabolismMerck Sharp and Dohme Corp.RahwayUSA