生理药代动力学模型的发展应用动态及其与其他建模方法的融合  

Development and application progress of physiologically based pharmacokinetic modeling and its combined use with other modeling methods

作　　者：陈文君[1] 阮邹荣[1] 相小强[2] CHEN Wenjun;RUAN Zourong;XIANG Xiaoqiang(Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University, Hangzhou 310009, Zhejiang, China;School of Pharmacy, Fudan University, Shanghai 201203, China)

机构地区：[1]浙江大学医学院附属第二医院临床药理中心,浙江杭州310009 [2]复旦大学药学院,上海201203

出　　处：《中国临床药理学与治疗学》2020年第3期299-305,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助项目(81473409)。

摘　　要：生理药代动力学(physiologically based pharmacokinetics,PBPK)是定量药理学的主要研究领域之一,其在新药研发和临床医疗实践的各个阶段均发挥着重要作用,包括药物早期开发阶段的人体药动学(pharmacokinetics,PK)预测、临床研究阶段考察各种生理和病理等因素对PK的影响、特殊人群剂量调整、药物相互作用等。近年来,PBPK模型在工业界的应用越来越广泛,监管机构也认可PBPK模型在药物研发中的积极指导作用。随着模型指导的药物研发的发展和普及,将PBPK模型与其他常用建模方法,包括群体药代动力学(population pharmacokinetics,PopPK)、药代动力学/药效动力学(pharmacokinetic/pharmacodynamic,PK/PD)模型和基于模型的Meta分析(model-based meta-analysis,MBMA)相融合可实现优势互补。本文简介了PBPK的起源、发展和应用现状,并对其与PopPK、PK/PD和MBMA的融合应用进展进行综述。Physiologically based pharmacokinetics(PBPK)is one of the main research fields of pharmacometrics,and it plays an important role at all the stages of drug development and clinical practice.In early drug discovery and development,human pharmacokinetics(PK)could be predicted by PBPK modeling using in silico,in vitro and preclinical in vivo data.During clinical studies,PBPK model could be used to investigate the effects of various physiological and pathological factors on PK,such as age,gender,liver/kidney impairment,and to guide dose adjustment of special population(pregnant women,children,etc.).Furthermore,PBPK modeling is now becoming more appealing with the ability to predict drug-drug interaction(DDI)in the case of co-administration of multiple drugs.In recent years,the application of PBPK modeling in industry has increased widely.Also,regulatory agencies have recognized the potential of PBPK and its impact on labeling recommendations.As the popularity of model-informed drug development,the combination of PBPK modeling with other commonly used modeling methods,such as population pharmacokinetics(PopPK),pharmacokinetic/pharmacodynamic(PK/PD)modeling and model-based meta-analysis(MBMA),has shown attractive advantages.In this paper,the origin and development,as well as the application status of PBPK are introduced briefly,and the application of PBPK modeling merged with PopPK,PK/PD and MBMA is reviewed.

关 键 词：生理药代动力学 群体药代动力学 药代动力学/药效动力学 基于模型的Meta分析 融合 

分 类 号：R969.1[医药卫生—药理学]