儿童生理药代动力学模型及其在儿科药物研究中的应用  

Physiologically based pharmacokinetic modeling for children and its application in pediatric drug research

作　　者：郑晓洁[1] 李思泽 袁雅文 金莎莎 李敏 相小强[2] ZHENG Xiao-jie;LI Si-ze;YUAN Ya-wen;JIN Sha-sha;LI Min;XIANG Xiao-qiang(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;School of Pharmacy,Fudan University,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201203 [2]复旦大学药学院,上海201203

出　　处：《药学学报》2020年第1期38-44,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81473409);上海市2018年度“科技创新行动计划”实验动物研究领域项目(18140900900);复旦大学附属中山医院闵行分院-复旦大学药学院战略合作自主研究课题融合基金(RO-MY201710)

摘　　要：生理药代动力学(physiologically based pharmacokinetic, PBPK)模型是预测药物在特殊人群中的药代动力学、药效学和安全性的重要工具。尤其对于儿童这类不易开展临床试验的人群, PBPK模型的应用更是能有效促进儿科药物的开发以及儿童的临床用药。目前, PBPK模型在儿科药物开发中的主要应用有以下几种:临床试验设计、药物相互作用(drug-drug interaction, DDI)的风险评估和儿童给药剂量的确立等。本综述简介了儿童生理药动学模型在儿科药物研究中的优越性,总结了PBPK模型如何实现从成人到儿童的外推,儿童生理药动学模型的理论基础,建模过程及所要注意的重要生理参数,列举了目前PBPK模型在儿科药物研究中的一些应用实例。最后简述了儿童PBPK模型当前的局限性和未来发展方向。Physiologically based pharmacokinetic(PBPK) modeling is an important tool to predict pharmacokinetic or pharmacodynamic profiles in special populations, especially in children and infants where designing and conducting clinical studies is difficult. The application of PBPK modeling can effectively promote the development of pediatric drugs and their clinical use. At present, PBPK modeling of pediatric populations is mainly applied in clinical trial design, drug-drug interaction(DDI) risk assessment, and dose selection in children. This review discusses the advantages of PBPK modeling in pediatric drug research and summarizes how to extrapolate a PBPK model from adults to children. The theoretical basis for pediatric PBPK models, the modelling process and important physiological parameters during the modeling process are introduced. Some successful applications of PBPK modeling in pediatric drug research and development are also presented. This review also analyzes the current limitations and future directions of pediatric PBPK modeling.

关 键 词：儿科药物 生理药代动力学模型 药物相互作用 

分 类 号：R969[医药卫生—药理学]