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Drug Transporters pp 261–283Cite as

P-glycoprotein: Tissue Distribution, Substrates, and Functional Consequences of Genetic Variations

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 201))

Abstract

P-glycoprotein (ABCB1, MDR1) belongs to the ABC transporter family transporting a wide range of drugs and xenobiotics from intra- to extracellular at many biological interfaces such as the intestine, liver, blood–brain barrier, and kidney. The ABCB1 gene is highly polymorphic. Starting with the observation of lower duodenal protein expression and elevated digoxin bioavailability in relation to the 3435C>T single nucleotide polymorphism, hundreds of pharmacokinetic and outcome studies have been performed, mostly genotyping 1236C>T, 2677G>T/A, and 3435C>T. Though some studies pointed out that intracellular concentrations of anticancer drugs, for example, within lymphocytes, might be affected by ABCB1 variants resulting in differential outcome, current knowledge of the functional significance genetic variants of ABC membrane transporters does not allow selection of a particular SNP to predict an individual’s pharmacokinetics.

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  1. Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Bldg. 30, 24105, Kiel, Germany

    Ingolf Cascorbi

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  1. Inst. Experimentelle und Klinische, Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstr. 17, Erlangen, 91054, Germany

    Martin F. Fromm

  2. Division of Clinical Pharmacology, University of Western Ontario, Windmere Road 339, London, N6A 5A5, Ontario, Canada

    Richard B. Kim

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Cascorbi, I. (2011). P-glycoprotein: Tissue Distribution, Substrates, and Functional Consequences of Genetic Variations. In: Fromm, M., Kim, R. (eds) Drug Transporters. Handbook of Experimental Pharmacology, vol 201. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14541-4_6

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