有机阴离子转运肽在药代动力学中的作用

Pharmacokinetics roles of organic anion transporting polypeptides

近年来,药物转运体在药物的吸收及代谢过程中发挥着重要的作用。有机阴离子转运肽(organic anion transporting polypeptides,OATPs)家族作为摄取转运体中的一员,由于其在肝、肠、肾等重要组织中的表达而影响着临床药物的药代动力学,尤其是OATP1B1,OATP1B3和OATP2B1。同时,众多临床药物被认为是OATP的底物药物(例如许多他汀类药物是OATP1B1的底物)。一些药物可能抑制OATP而导致药物相互作用(例如环孢素A)。此外,由OATP介导的基因多态性也导致了某些药物显著的个体差异。本文重点评述OATP家族不同成员在人体内的表达及其底物、OATP基因多态性、OATP介导的药物相互作用及其在临床药物的药动学与药效学中的作用。

During the recent years, drug transporters have been known to play an increasingly important role in drug absorption and metabolism. Organic anion transporting polypeptides（OATPs）, particularly OATP1B1, OATP1B3 and OATP2B1, are being increasingly recognized as important factors in governing the pharmacokinetics of clinical medicine because of their expression in critical tissues such as the liver, intestine and kidneys. Meanwhile, a variety of clinically used drugs have been identified as substrates of OATP transporters（e. g. many statins are substrates of OATP1B1）. Some drugs may inhibit OATP transporters（e. g. cyclosporine A）, causing pharmacokinetic drug-drug interactions. Moreover, genetic variability in genes encoding OATP transporters can result in marked inter-individual differences in pharmacokinetics. The aim of our work was to review the expression of OATP transporters in human and their substrates, drug-drug interactions and genetic polymorphisms, as well as their roles in drug pharmacokinetics and pharmacological efficacy.