基于生理的药代动力学模型在创新药临床研发中的应用进展

Application progress of physiologically-based pharmacokinetic model in clinical development of novel molecular entities

基于生理的药代动力学模型(PBPK)可通过整合人体生理系统参数、药物理化性质和机制性药代动力学数据以提早预测人体内的药物药代动力学特征。借用该方法预测新条件(新给药方案、新人群特征)下药物药代动力学特征,促进更有策略、更安全、更经济地进行临床开发。目前,PBPK已经在美国、欧盟的创新药开发中得到广泛应用,并有相关指南出台指引PBPK研究,本文将综述PBPK在创新药临床研发的应用进展、研究策略及相关指南要求,以期为我国创新药临床开发提供策略支持。

By integrating human physiological parameters, drug chemi- cal/physical data, and drug mechanistic pharmacokinetic data, physio- logically -based pharmacokinetics model （PBPK） can be used to predict pharmacokinetic/pharmacodynamics characteristics in subjects under va- rious clinical conditions （e. g. different dose regimen, specific popula- tion）. As such, PBPK prediction supports efficient, faster and safe clini- cal development of novel molecular entities. Recently, PBPK analyses have been extensively applied in new drug development in US and Eu- rope, where relevant guidance documents have been released to direct PBPK study. In this review, we will introduce the application of PBPK model in clinical development of new drug and hopefully to update know- ledge in PBPK study and support new drug development in our country.