Membrane transporters in drug development

作者：Giacomini Kathleen M^*; Huang Shiew Mei; Tweedie Donald J; Benet Leslie Z; Brouwer Kim L R; Chu Xiaoyan; Dahlin Amber; Evers Raymond; Fischer Volker; Hillgren Kathleen M; Hoffmaster Keith A; Ishikawa Toshihisa; Keppler Dietrich; Kim Richard B; Lee Caroline A; Niemi Mikko; Polli Joseph W; Sugiyama Yuicchi; Swaan Peter W; Ware Joseph A; Wright Stephen H; Yee Sook Wah; Zamek Gliszczynski Maciej J; Zhang Lei

来源：Nature Reviews Drug Discovery, 2010, 9(3): 215-236.

DOI：10.1038/nrd3028

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.

• 出版日期2010-3