Nat Rev Drug Discov. 2010 Mar;9(3):215-36. 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.
膜转运体可显著影响药物的药代动力学、安全性和疗效特征。这给药物开发带来了几个关键问题，包括哪些转运体在药物吸收和处置中具有临床重要性，以及哪些体外方法适合研究药物与这些转运体的相互作用。此外，什么标准应触发后续临床研究，如果需要，应进行哪些临床研究。在本文中，我们提供了国际转运体联合会对这些问题的建议，并提出了决策树，旨在帮助指导目前公认最重要的药物转运体相互作用的临床研究。这些建议通常旨在支持新药申请的临床开发和申报。总体而言，建议转运体研究的时间应根据疗效、安全性和临床试验入组问题（例如排除和纳入标准）、以及对药物分子吸收、分布、代谢和排泄特性的进一步了解以及药物标签所需的信息来驱动。
