Ghibellini Giulia, Leslie Elaine M, Brouwer Kim L R
School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Mol Pharm. 2006 May-Jun;3(3):198-211. doi: 10.1021/mp060011k.
Determining the biliary clearance of drugs in humans is very challenging because bile is not readily accessible due to the anatomy of the hepatobiliary tract. The collection of bile usually is limited to postsurgical patients with underlying hepatobiliary disease. In healthy subjects, feces typically are used as a surrogate to quantify the amount of drug excreted via nonurinary pathways. Nevertheless, it is very important to characterize hepatobiliary elimination because this is a potential site of drug interactions that might result in significant alterations in systemic or hepatic exposure. In addition to the determination of in vivo biliary clearance values of drugs, the availability of in vitro models that can predict the extent of biliary excretion of drugs in humans may be a powerful tool in the preclinical stages of drug development. In this review, recent advances in the most commonly used in vivo methods to estimate biliary excretion of drugs in humans are outlined. Additionally, in vitro models that can be employed to investigate the molecular processes involved in biliary excretion are discussed to present an updated picture of the new tools and techniques that are available to study the complex processes involved in hepatic drug transport.
确定药物在人体中的胆汁清除率极具挑战性，因为由于肝胆管的解剖结构，胆汁不易获取。胆汁的收集通常仅限于患有潜在肝胆疾病的术后患者。在健康受试者中，粪便通常被用作替代物来量化通过非尿液途径排泄的药物量。然而，表征肝胆清除非常重要，因为这是药物相互作用的一个潜在部位，可能导致全身或肝脏暴露的显著改变。除了确定药物的体内胆汁清除率值外，能够预测药物在人体中胆汁排泄程度的体外模型的可用性可能是药物开发临床前阶段的一个有力工具。在这篇综述中，概述了用于估计人体药物胆汁排泄的最常用体内方法的最新进展。此外，还讨论了可用于研究参与胆汁排泄的分子过程的体外模型，以呈现可用于研究肝脏药物转运复杂过程的新工具和技术的最新情况。
