Division of Applied Regulatory Science, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Expert Opin Drug Discov. 2024 Oct;19(10):1247-1257. doi: 10.1080/17460441.2024.2387790. Epub 2024 Aug 6.
Determining whether a new drug is a substrate, inhibitor or inducer of efflux or uptake membrane transporters has become a routine process during drug discovery and development. assays are utilized to establish whether a new drug has the potential to be an object (substrate) or precipitant (inhibitor, inducer) in transporter-mediated clinical drug-drug interactions. The findings from these experiments are then used to determine whether further drug interaction studies are necessary for a new drug.
This article provides an update on transporter assays, focusing on new uses of transfected cells, time-dependent inhibition, transporter induction, and complex model systems.
The newer assays add to the toolbox in defining new drugs as transporter substrates, inhibitors, or inducers. Complex models such as spheroids, organoids, and microphysiological systems require standardization and further research with model transporter substrates and inhibitors. In drug discovery, the more traditional transporter assays may be employed as substrate and inhibitor screening assays. In drug development, more complex cell models can be employed in later drug development to better understand how transporter(s) are involved in the absorption, distribution, and excretion of new drugs.
在药物发现和开发过程中，确定新药是否为外排或摄取膜转运体的底物、抑制剂或诱导剂已成为常规流程。测定法用于确定新药是否有成为转运体介导的临床药物相互作用的对象（底物）或沉淀剂（抑制剂、诱导剂）的潜力。这些实验的结果用于确定是否需要进一步进行新药的药物相互作用研究。
本文提供了转运体测定法的最新进展，重点介绍了转染细胞的新用途、时变抑制、转运体诱导以及复杂模型系统。
较新的测定法增加了定义新药为转运体底物、抑制剂或诱导剂的工具。类器官、微生理系统等复杂模型需要与模型转运体底物和抑制剂进行标准化和进一步研究。在药物发现中，更传统的转运体测定法可以用作底物和抑制剂筛选测定法。在药物开发中，更复杂的细胞模型可在后期药物开发中使用，以更好地了解转运体如何参与新药的吸收、分布和排泄。
