生理药代动力学模型预测药物不良反应的研究进展  

Research progress of physiologically‑based pharmacokinetic model for predicting adverse drug reactions

作　　者：郑澳乐 李晓瑜 何庆烽 相小强[1] Zheng Aole;Li Xiaoyu;He Qingfeng;Xiang Xiaoqiang(School of Pharmacy,Fudan University,Shanghai 201203,China;College of Mechanical and Vehicle Engi-neering,Chongqing University,Chongqing 400044,China)

机构地区：[1]复旦大学药学院,上海201203 [2]重庆大学机械与运载学院,重庆400044

出　　处：《药物不良反应杂志》2023年第7期430-436,共7页Adverse Drug Reactions Journal

基　　金：国家自然科学基金国际合作项目(82011540409)。

摘　　要：不论在新药研发阶段还是药品上市后临床应用阶段,药物安全性问题始终是应首要关注的问题,也是药物研发失败甚至上市后药品退市的主要原因。生理药代动力学(PBPK)模型不仅可以常规预测人体血浆药代动力学,还可以预测药物在不同组织中浓度分布,是预测新药不良反应的重要工具,已逐渐受到药品监管部门的重视。本文简述了PBPK模型用于预测药物肾脏毒性、心脏毒性、神经毒性的最新研究进展和应用情况,为新药研发中不良反应的早期预测和药物临床合理应用提供参考。Drug safety is always the primary concern in both the stage of new drug development and the post‑marketing clinical application stage,and it is also the main reason for drug development failure and even post‑marketing drug withdrawal.The physiologically‑based pharmacokinetic(PBPK)model can not only routinely predict the human plasma pharmacokinetics,but also predict the concentration distribution of drugs in different tissues,which has become an important tool for predicting the adverse reactions of new drugs and has gradually attracted the attention of drug regulatory authorities.In this article,the latest prog‑ress and application of the PBPK model for predicting drug‑induced nephrotoxicity,cardiotoxicity,and neu‑rotoxicity are briefly reviewed to provide references for early prediction of adverse drug reactions in new drug development and rational clinical use of drugs.

关 键 词：生理药代动力学模型 药物相关副作用和不良反应 肾脏毒性 心脏毒性 神经毒性 

分 类 号：R969.1[医药卫生—药理学]