幼龄动物药物代谢研究进展  

Progress in research on drug metabolism in juvenile animals

作　　者：李广路 张文鹏 吴纯启 庄笑梅 张天宏 王全军 LI Guang-lu;ZHANG Wen-peng;WU Chun-qi;ZHUANG Xiao-mei;ZHANG Tian-hong;WANG Quan-jun(State Key Laboratory of Medical Countermeasures and Toxicology,Institute of Pharmacology and Toxicology,National Beijing Center for Drug Safety Evaluation and Research,,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]军事医学研究院毒物药物研究所,抗毒物药物与毒理学国家重点实验室,国家北京药物安全评价研究中心,北京100850

出　　处：《中国新药杂志》2022年第4期329-336,共8页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项资助项目(2018ZX09721003-001-005,2018ZX09711003-007,2018ZX09201017-003)。

摘　　要：近年来,随着儿童药物研发和儿童用药越来越得到重视,非临床幼龄动物研究(juvenile animals study,JAS)作为儿科药物研发过程中重要组成部分也获得了更多的关注。由于儿童的生理发育、体内药物处置和药效毒理作用等方面与成人差异显著,采用幼龄动物开展儿科新药的非临床药物代谢和安全性评价在儿童药物评价方面尤为重要。国内外药品监管部门已经制定了有关安全性评价方面的指导原则,但对于幼龄动物代谢方面的研究,国内外都还处于探索阶段。本文总结了国内外幼龄动物评价研究相关指导原则要求和研究开展情况,详细介绍了幼龄动物器官水平药物代谢能力发育研究情况、幼龄动物药物代谢、毒物代谢研究的重要关注点,以及基于生理药动学(PBPK)模型在幼龄动物药物代谢和毒理学研究方面的应用,以期为儿童药物研发提供技术支持和参考。In recent years,with the increasing attention to pediatric drugs research and application,non-clinical juvenile animal study(JAS)has become an irreplaceable part of this field.In view of the significant difference between juveniles and adults for physiological development,internal drug disposal,pharmacodynamic and toxicological effects,it’s particularly important to carry out non-clinical metabolism and safety evaluation of pediatric drugs in juvenile animals.The administrative agencies have made series guidelines about safety evaluation,but it is still in exploration worldwide for JAS.This article reviewed the domestic and foreign guidelines for the evaluation of juvenile animals.It also introduced in detail the latest research on JAS including juvenile animals’potential to metabolize drugs at organ level,the main focus of pharmacokinetic(PK)and toxicokinetic(TK)study,and the application of physiologically based pharmaco kinetic(PBPK)model in JAS,thus to provide reference for pediatric drugs research and development.

关 键 词：幼龄动物 药物毒物代谢 儿童药物 生理药动学模型 

分 类 号：R985[医药卫生—药品]