In Vitro Techniques to Study Transporter-Based DDI

Abstract

In recent years numerous examples have been published where pharmacokinetic drug–drug interactions could be ascribed to inhibition
of uptake or efflux drug transporters in, for instance, the liver and kidney. In drug discovery and development, it therefore
has become increasingly important to identify the propensity of drug candidates to cause such interactions, either as a victim
or perpetrator. In this chapter, we describe the status of in vitro methodologies currently applied to predict the propensity
of drug candidates to be a victim or perpetrator in DDIs due to inhibition of transporter activity. Assay systems discussed
are recombinant cell lines expressing transporters, primary cells such as hepatocytes, and membrane vesicles. Special focus
is on transporters expressed in liver and kidney, with the exception of ABCB1 which is covered elsewhere in this book. In
addition, we present the current understanding of how data generated in these systems can be used to predict DDI potential
of drug candidates.