基于机制的生理药动-药效学模型研究进展  

Recent Research Advances in Mechanistic Physiologically Based Pharmacokinetic-Pharmacodynamic Models

作　　者：徐瑞娟[1,2] 杨进波[3] 杨劲[1] 

机构地区：[1]中国药科大学药物代谢研究中心,江苏南京210009 [2]南京大学医学院附属鼓楼医院药学部,江苏南京210008 [3]国家食品药品监督管理局药品审评中心,北京100038

出　　处：《药学进展》2014年第11期801-808,共8页Progress in Pharmaceutical Sciences

摘　　要：生理药动-药效学模型通过对生物学过程的描述,可预测体内药物的吸收、分布、代谢、排泄以及进一步的生理生化反应。这类模型是通过已知的生化/生理基础来构建,采用了一种"自下而上"的建模方法,并利用数学方法对生理过程及药物的作用机制作出准确的描述。其中药效学部分,根据预测目的和药物作用的复杂性,可进一步分为基于经验的和基于机制的效应模型,这两种模型均可与基于机制的生理药动学模型相连接,最终预测药物的体内处置和效应。基于机制的生理药动-药效学模型的优势在于:可外推性、新的影响因素的可纳入性以及可用于未知领域的预测等。随着实验技术的不断革新,药物作用机制的逐渐明确,这类模型越来越多的被成功应用于药物研发及风险评估中。综述生理药动-药效学模型的构建策略与分类以及在药物研发和风险评估中的应用研究。Physiologically based pharmacokinetic-pharmacodynamic （PBPK/PD） models can be used to predict absorption, distribution, metabolism, excretion and further physicological and biological effect of drugs in vivo by characterizing the biological process. On the basis of physieology and biology, these models are developed by a modeling method usually described as ＂bottom-up＂, using mathematic methods to describe accurately the physiological process and the mechanism of action of drugs. The pharmacodynamic models can be further divided into empirical-based and mechanism-based models, both of which can be linked with the mechanistic PBPK model further to predict disposition and effect of drugs in vivo. The advantages of mechanistic PBPK/PD models are as follows： able to be used in extrapolation, able to include new factors and able to predict scenarios in new situation never experienced before. With more and more innovative experimental techniques and knowledge of the mechanisms of action of drugs, PBPK/PD models have been successfully applied in the drug research and development and risk assessment. The construction strategy and classification of PBPK/PD models as well as their application in the drug research and development and risk assessment were reviewed.

关 键 词：生理药动学模型 药效学模型 系统生物学 基于机制模型 药物研发 风险评估 

分 类 号：R96[医药卫生—药理学]