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.
Pharmacol Ther. 2022 Oct;238:108268. doi: 10.1016/j.pharmthera.2022.108268. Epub 2022 Aug 20.
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.
有机阳离子转运体（OCT）、有机阴离子转运多肽（OATP）和有机阴离子转运体（OAT）属于溶质载体（SLC）家族，在将内源性化合物和药物摄取到肝细胞和其他细胞类型中发挥着重要作用。这些转运体表达和活性的个体间差异很大，导致药物药代动力学和药物反应的个体间差异。因此，阐明影响膜转运体表达和功能的机制非常重要。这些机制包括转录调控、疾病相关调控和遗传变异。在这篇综述中，我们将总结已克隆的肝 OCT、OATP 和 OAT 的分子功能和底物谱的最新知识，并讨论对可变表达和功能的理解的最新进展。最后，将介绍这些转运体的遗传变异对药物暴露的作用及其对个体药物反应的影响。
