In Vitro Techniques to Study Transporter-Based DDI



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.


Efflux Transporter Uptake Transporter Recombinant Cell Line MDCKII Cell Transporter Expression Level 
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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Metabolism and Pharmacokinetics, Merck & Co.In Vitro TechnologiesRahwayUSA
  2. 2.Department of Drug Metabolism and Pharmacokinetics, Merck & Co.In Vitro TechnologiesRahwayUSA

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