肝脏“代谢-转运互作”及其对药物药代动力学、疗效和毒性影响的研究进展

肝脏是药物代谢和排泄的主要器官。肝脏药物代谢酶和膜转运体对肝细胞内药物处置及其临床疗效和毒性产生重要影响。近年来,国内外学者发现被称为"代谢-转运互作"的动力学现象,其对药物药代动力学(生物利用度)、药物相互作用具有显著影响。药物代谢酶与转运体间的功能相互作用是目前药物代谢和药代动力学研究的热点之一。本文对肝脏代谢-转运互作进行了探究,并系统阐述了这种互作对药物(特别是Ⅱ相药物代谢)的药物相互作用、药代动力学、临床疗效和毒性反应的影响。今后应进一步阐明肝脏代谢-转运互作机制,有助于研究体内药物处置及药物相互作用,为临床合理用药提供新思路和新技术。

Recent advances in hepatic “metabolism-transport interplay” and its effect on drug pharmacokinetics,clinical efficacy and toxicity

The liver is the major organ of drug metabolism and excretion. The drug-metabolizing enzymes and membrane transporters in the liver that influence hepatic intracellular concentrations can have a major impact on the overall disposition of drugs as well as their efficacy and toxicity. In recent years, scholars at home and abroad have discovered the kinetic phenomenon known as "metabolism-transport interplay", which has a significant impact on pharmacokinetics (bioavailability) and drug interactions. Functional interplay between transporters and drug-metabolizing enzymes is currently one of the hottest topics in the field of drug metabolism and pharmacokinetics. The paper reviewed the hepatic metabolism-transport interplay, which can significantly affect drug interactions, pharmacokinetics, clinical efficacy and toxicity of drugs (especially phase Ⅱ drug metabolism). The mechanism of metabolism-transport interplay in the liver will be further elucidated in the future, which will be helpful to investigate the drug disposition and drug interaction in vivo, and provide new ideas and technologies for rational drug use in clinical practice.