Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, USA.
Clin Pharmacol Ther. 2012 Nov;92(5):599-612. doi: 10.1038/clpt.2012.79. Epub 2012 Sep 5.
Detailed knowledge regarding the influence of hepatic transport proteins on drug disposition has advanced at a rapid pace over the past decade. Efflux transport proteins located in the basolateral and apical (canalicular) membranes of hepatocytes play an important role in the hepatic elimination of many endogenous and exogenous compounds, including drugs and metabolites. This review focuses on the role of these efflux transporters in hepatic drug excretion. The impact of these proteins as underlying factors for disease is highlighted, and the importance of hepatic efflux proteins in the efficacy and toxicity of drugs is discussed. In addition, a brief overview of methodology to evaluate the function of hepatic efflux transport proteins is provided. Current challenges in predicting the impact of altered efflux protein function on systemic, intestinal, and hepatocyte exposure to drugs and metabolites are highlighted.
在过去的十年中，人们对肝转运蛋白对药物处置的影响的了解取得了飞速的发展。位于肝细胞基底外侧和顶膜（胆小管）的外排转运蛋白在许多内源性和外源性化合物（包括药物和代谢物）的肝消除中发挥着重要作用。这篇综述重点介绍了这些外排转运蛋白在肝药物排泄中的作用。强调了这些蛋白作为疾病基础因素的作用，并讨论了肝外排蛋白在药物疗效和毒性中的重要性。此外，还简要概述了评估肝外排转运蛋白功能的方法学。强调了预测改变外排蛋白功能对药物和代谢物全身、肠道和肝细胞暴露影响方面所面临的挑战。
