ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2

Author:

Kerb Reinhold1,Hoffmeyer Sven1,Brinkmann Ulrich2

Affiliation:

1. Epidauros Biotechnology, Pharmacogenetics Labs., Am Neuland 1, D-82347, Bernried, Germany.

2. Epidauros Biotechnology, Pharmacogenetics Labs., Am Neuland 1, D-82347, Bernried, Germany. uli@epidauros.com

Abstract

Transport by ATP-dependent efflux pumps, such as P-glycoprotein (PGP) and multi-drug resistance related proteins (MRPs), influences bioavailability and disposition of drugs. These efflux pumps serve as defence mechanisms and determine bioavailability and CNS concentrations of many drugs. However, despite the fact that substantial data have been accumulated on the structure, function and pharmacological role of ABC transporters and even though modification of PGP function is an important mechanism of drug interactions and adverse effects in humans, there is a striking lack of data on variability of the underlying genes. This review focuses on the human drug transporter proteins PGP (MDR1) and the multi-drug resistance proteins MRP1 and MRP2. An overview is provided of pharmacologically relevant genetic, structural and functional data as well as on hereditary polymorphisms, their phenotypical consequences and pharmacological implications.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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