Hepatic solute carrier transporters and drug therapy: Regulation of expression and impact of genetic variation.

Anne T Nies, Elke Schaeffeler, Matthias Schwab

Journal: Pharmacology & therapeutics 2022;238():108268

PMID: 35995278

Full Text on Elsevier Science View on PubMed

Abstract

Organic cation transporters (OCT), organic anion transporting polypeptides (OATP) and organic anion transporters (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 expression 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 expression and function. Finally, the role of genetic variation in these transporters on drug exposure will be presented with implications for individual drug response.

Address: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen, Tuebingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University of Tuebingen, Tuebingen, Germany. Electronic address: [email protected].; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen, Tuebingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University of Tuebingen, Tuebingen, Germany.; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen, Tuebingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University of Tuebingen, Tuebingen, Germany; Departments of Clinical Pharmacology, and of Biochemistry and Pharmacy, University of Tuebingen, Tuebingen, Germany.

DOI: 10.1016/j.pharmthera.2022.108268

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MeSH Terms: Cations, Genetic Variation, Humans, Liver, Organic Anion Transporters, Peptides