Pharmacogenomics of human OATP transporters

J König, A Seithel, U Gradhand, MF Fromm - … -Schmiedeberg's archives of …, 2006 - Springer
J König, A Seithel, U Gradhand, MF Fromm
Naunyn-Schmiedeberg's archives of pharmacology, 2006Springer
Organic anion transporting polypeptides (OATPs) mediate the uptake of a broad range of
compounds into cells. Substrates for members of the OATP family include bile salts,
hormones, and steroid conjugates as well as drugs like the HMG-CoA-reductase inhibitors
(statins), cardiac glycosides, anticancer agents like methotrexate, and antibiotics like
rifampicin. OATPs are expressed in a variety of different tissues, including intestine, liver,
kidney, and brain, suggesting that they play a critical role in drug absorption, distribution …
Abstract
Organic anion transporting polypeptides (OATPs) mediate the uptake of a broad range of compounds into cells. Substrates for members of the OATP family include bile salts, hormones, and steroid conjugates as well as drugs like the HMG-CoA-reductase inhibitors (statins), cardiac glycosides, anticancer agents like methotrexate, and antibiotics like rifampicin. OATPs are expressed in a variety of different tissues, including intestine, liver, kidney, and brain, suggesting that they play a critical role in drug absorption, distribution, and excretion. The identification and functional characterisation of naturally occurring variations in genes encoding human OATP (SLCO) family members is in the focus of transporter research. As a result of their broad substrate spectrum and their wide tissue distribution, altered transport characteristics or protein localisation can contribute significantly to interindividual variations of drug effects. The analysis of the consequences of genetic variations in genes encoding transport proteins may, therefore, contribute to a better understanding of interindividual differences in drug effects and to individualise treatment regimens with drugs that are substrates for human OATP proteins. In this review, we summarise the current knowledge on genetic variations in transporter genes encoding human OATP family members and their functional consequences analysed by in vitro and in vivo studies.
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