Membrane transporters in drug development

Authors

Kathleen M. Giacomini, University of California, San Francisco
Shiew Mei Huang, Food and Drug Administration
Donald J. Tweedie, Boehringer Ingelheim Pharmaceuticals, Inc.
Leslie Z. Benet, University of California, San Francisco
Kim L.R. Brouwer, The University of North Carolina at Chapel Hill
Xiaoyan Chu, Merck & Co., Inc.
Amber Dahlin, University of California, San Francisco
Raymond Evers, Merck & Co., Inc.

Document Type

Article

Publication Date

3-1-2010

Journal

Nature Reviews Drug Discovery

Volume

9

Issue

3

First Page

215

Last Page

236

URL with Digital Object Identifier

10.1038/nrd3028

Abstract

Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling. © 2010 Macmillan Publishers Limited.