The University of Tokyo, Japan.
Drug Metab Rev. 2010 Aug;42(3):539-50. doi: 10.3109/03602530903491824.
Hepatocytes express various transporters in the sinusoidal and canalicular membrane, which mediate hepatic uptake and canalicular efflux, forming directional transport from the sinusoid to the bile. Drug-drug interactions and genetic polymorphisms of the transporters are known to cause variations in transporter function. This review focuses on pharmacokinetic modeling of hepatobiliary transport of drugs to explain the alteration of the disposition of drugs caused by such variations, based on the clearance concept. For modeling and simulation, pravastatin and dibromosulfophthalein have been used as model compounds which are known to undergo transpoter-mediated hepatic uptake followed by biliary excretion. Pharmacokinetic modeling of hepatobiliary transport illustrates the concept of the rate-determining process in overall hepatobiliary transport.
肝细胞在窦状膜和胆管膜表达各种转运体，介导肝摄取和胆管排泄，形成从窦状隙向胆汁的方向转运。转运体的药物-药物相互作用和遗传多态性已知会引起转运体功能的变化。本综述重点介绍药物肝胆转运的药代动力学模型，基于清除率概念，解释这些变化引起的药物处置变化。对于建模和模拟，普伐他汀和二溴磺酚酞已被用作模型化合物，已知它们通过转运体介导的肝摄取，然后经胆汁排泄。肝胆转运的药代动力学模型说明了总体肝胆转运中速率决定过程的概念。
