评估新药候选药物与转运蛋白的相互作用，或者作为基底，抑制剂,或诱导物，不是简单的事情。有许多临床相关的转运蛋白，截至2020年，FDA提交的评估多达9项，EMA评估多达11项。此外,如果一种化合物是一种转运蛋白的底物或抑制剂，其他运输商也是如此。实际上没有特定的底物或抑制剂，大概是因为药物转运蛋白的特异性如此广泛和重叠，甚至更少的临床相关探针可用于评估人类的转运蛋白功能。在一些运输者的情况下，建议使用一个以上的测试系统和/或一个以上的探针底物对NCE进行评估,以说服自己(和监管机构)不需要进行临床药物相互作用研究.最后,每个测试系统都有自己独特的优点和缺点。人们必须欣赏可用工具的细微差别(测试系统，探针基板,等。），以选择最相关的工具进行研究，并设计最佳的体外实验。在这一章中,几个例子被用来说明外排和摄取转运蛋白体外数据的成功解释。本章中提供的一些数据在本书编写时尚未发表。本章中包含的内容是为读者提供转运蛋白动力学的复杂性。
Assessing the interactions of a new drug candidate with transporters, either as a substrate, inhibitor, or inducer, is no simple matter. There are many clinically relevant transporters, as many as nine to be evaluated for an FDA submission and up to 11 for the EMA as of 2020. Additionally, it is likely that if a compound is a substrate or inhibitor of one transporter, it will be so for other transporters as well. There are practically no specific substrates or inhibitors, presumably because the specificities of drug transporters are so broad and overlapping, and even fewer clinically relevant probes that can be used to evaluate transporter function in humans. In the
case of some transporters, it is advisable to evaluate an NCE with more than one test system and/or more than one probe substrate in order to convince oneself (and regulatory authorities) that a clinical drug interaction study is not warranted. Finally, each test system has its own unique set of advantages and disadvantages. One has to appreciate the nuances of the available tools (test systems, probe substrates, etc.) to select the most relevant tools for the study and design the optimal in vitro experiment. In this chapter, several examples are used to illustrate the successful interpretation of in vitro data for both efflux and uptake transporters. Some data presented in this chapter are unpublished at the time of the compilation of this book. It has been included in this chapter to provide a sense of the complexities in transporter kinetics to the reader.
