肝脏转运体介导药物相互作用的研究进展

Drug-drug interactions mediated by hepatic transporters

转运体是位于细胞膜上的功能性膜蛋白,在肝脏表达广泛,其生理功能是将大多数内源性物质、外源性化学异物或药物等摄取进入肝脏,在肝脏经过一定的代谢转化,最终将其经胆汁排至肝外.肝脏转运体在药物肝胆转运中起重要作用,转运体与药物在肝脏的摄取、代谢及排泄等功能密切相关,转运体的功能抑制、缺失是生理疾病和药物之间相互作用的重要因素.临床联合应用与转运体有关的药物时可能发生由转运体介导的药物相互作用,如西立伐他汀不良反应事件.本文从肝脏转运体的抑制、诱导和单核苷酸多态性出发,对由肝脏转运体引起的药物相互作用作一综述.

Transporters are a class of functional membrane proteins that are extensively expressed in the liver and are involved in the transport of a wide variety of compounds including endogenous and xenobiotic substances from the bloodstream into hepatocytes. And then, these parent sub stances are metabolized in the liver and excreted into bile. Hepatic transporters play important roles in the hepatic transport process of drugs, including the uptake of drugs from blood into hepatocytes or the effiux of drugs into bile. The uptake, metabolism and excretion of drugs in the liver are related to hepatic transporters. Decline or loss of transporting function of trans- porters caused by gene mutations is related with a variety of liver diseases. Drug-drug interaction may be induced when one drug （as a substrate or inhibitor of hepatic transporters） is co-admin-istered simultaneously with another in clinical practice, such as adverse events of cerivastatin. In this paper, we review the potential drug-drug interactions mediated by hepatic transporters.