期刊
PHARMACOLOGY & THERAPEUTICS
卷 238, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2022.108268
关键词
SLCO; SLC22; Genetic variants; Regulation; Pharmacogenomics; Drug response
资金
- Robert Bosch Stiftung (Stuttgart, Germany)
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy-EXC [2180-390900677]
Organic cation transporters (OCT), organic anion transporting polypeptides (OATP), and organic anion transporters (OAT) from the solute carrier (SLC) family play a crucial role in the uptake of endogenous compounds and drugs. The variability in expression and activity of these transporters leads to interindividual differences in drug pharmacokinetics and response. This review provides an overview of the molecular functions and substrate profiles of hepatic OCTs, OATPs, and OATs, as well as recent advances in understanding their variable expression and function. The impact of genetic variation in these transporters on drug exposure and individual drug response is also discussed.
Organic cation transporters (OCT), organic anion transporting polypeptides (OATP) and organic anion trans-porters (OAT) from the solute carrier (SLC) family play an essential role in the uptake of endogenous compounds and drugs into the hepatocytes and other cell types. The well-documented interindividual variability of expres-sion and activity of these transporters translates into interindividual variability in drug pharmacokinetics and drug response. It is therefore important to elucidate mechanisms affecting membrane transporter expression and function. These mechanisms include transcriptional regulation, disease-dependent regulation and genetic variation. In this review, we will summarize the current knowledge of the molecular functions and substrate profiles of cloned hepatic OCTs, OATPs and OATs and discuss recent advances in understanding variable expres-sion and function. Finally, the role of genetic variation in these transporters on drug exposure will be presented with implications for individual drug response.(c) 2022 Elsevier Inc. All rights reserved.
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