Pharmacokinetic assessment of multiple ATP-binding cassette transporters: the power of combination knockout mice.
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.
Lagas
Jurjen S
JS
Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Vlaming
Maria L H
ML
Schinkel
Alfred H
AH
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D004364:Pharmaceutical Preparations / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D004364:Pharmaceutical Preparations