Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
DMPK, Oncology iMed, AstraZeneca R&D Alderley Park, Macclesfield, Cheshire, UK.
AAPS J. 2016 Sep;18(5):1067-1081. doi: 10.1208/s12248-016-9942-x. Epub 2016 Jun 30.
The programme for the 2015 AAPS Annual Meeting and Exhibition (Orlando, FL; 25-29 October 2015) included a sunrise session presenting an overview of the state-of-the-art tools for in vitro-in vivo extrapolation (IVIVE) and mechanistic prediction of renal drug disposition. These concepts are based on approaches developed for prediction of hepatic clearance, with consideration of scaling factors physiologically relevant to kidney and the unique and complex structural organisation of this organ. Physiologically relevant kidney models require a number of parameters for mechanistic description of processes, supported by quantitative information on renal physiology (system parameters) and in vitro/in silico drug-related data. This review expands upon the themes raised during the session and highlights the importance of high quality in vitro drug data generated in appropriate experimental setup and robust system-related information for successful IVIVE of renal drug disposition. The different in vitro systems available for studying renal drug metabolism and transport are summarised and recent developments involving state-of-the-art technologies highlighted. Current gaps and uncertainties associated with system parameters related to human kidney for the development of physiologically based pharmacokinetic (PBPK) model and quantitative prediction of renal drug disposition, excretion, and/or metabolism are identified.
2015 年 AAPS 年会和展览（佛罗里达州奥兰多；2015 年 10 月 25-29 日）的计划包括一个日出会议，概述了用于体外-体内外推（IVIVE）和肾脏药物处置的机制预测的最新工具。这些概念基于为预测肝脏清除率而开发的方法，考虑了与肾脏相关的生理缩放因子以及该器官的独特而复杂的结构组织。生理相关的肾脏模型需要许多参数来对过程进行机制描述，并辅以有关肾脏生理学（系统参数）和体外/计算机药物相关数据的定量信息。本综述扩展了会议期间提出的主题，并强调了高质量的体外药物数据在适当的实验设置和稳健的系统相关信息对于成功进行肾脏药物处置的 IVIVE 的重要性。总结了用于研究肾脏药物代谢和转运的不同体外系统，并强调了涉及最先进技术的最新发展。确定了与人类肾脏相关的系统参数开发生理相关药代动力学（PBPK）模型和定量预测肾脏药物处置、排泄和/或代谢方面的当前差距和不确定性。
