Pharmacokinetic Assessment of Multiple ATP-binding Cassette Transporters: The Power of Combination Knockout Mice

  1. Jurjen S. Lagas1,
  2. Maria L.H. Vlaming1 and
  3. Alfred H. Schinkel
  1. Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

Abstract

A TP-binding cassette (ABC) multidrug transporters are cellular efflux pumps with broad and often widely overlapping substrate specificities. They can have a major impact on the pharmacokinetics and hence overall pharmacological behavior of many drugs. To study their separate roles and functional overlap, or complementarity, a collection of mice deficient in two or more ABC transporters has been generated. This review discusses recent findings obtained with these models, focusing on pharmacokinetic studies with a number of clinically relevant drugs. In addition, the characterization of these mice and some physiological aspects of ABC multidrug transporters are addressed.

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