摘要
非临床安全性评价是儿科药物研发的一个必要和独特的部分。儿童用药的安全性问题与成人用药相比具有独特性,不仅与儿童器官系统的发育密切相关,而且儿童药动学特性(吸收、分布、代谢和排泄)的变化常常会导致暴露量和毒性反应不同于成人。目前,人们通过幼龄动物毒理学试验来评估药物在儿童用药的安全性。幼龄动物毒理学试验有许多需要特殊考虑的地方,无标准的试验设计,需要具体问题具体分析来确定相应的试验设计。本文介绍国外对幼龄动物毒理学试验的经验,介绍了不同动物种属之间器官发育的比较,重点阐述了幼龄动物试验设计和实施的特殊关注要点,包括总体试验设计、评价指标的选择、种属选择、剂量选择、动物起始年龄和给药期限、同窝幼仔的分组考虑、一些实施问题试验数据分析与评价等。通过以上国外经验的介绍,期望对国内研发者提供参考。
Non-clinical safety evaluation is an essential and unique part of the pediatric drug development.Pediatric safety issues are unique and related to organ system development and changes in absorption,distribution,metabolism and excretion with age,which leads to differences in exposureand toxicity profile from that seen in adults. Juveniles are not little adults,so many special considerations are needed when design and conduct juvenile animal studies（JAS）. JAS design has not standard study design,and should be on a case-by-case basis to support the pediatric clinical plan. This paper introduces some foreign experiences of JAS,and focuses on the considerations of designing and conducting of JAS,including overall design,study endpoints,species selection,dose selection,age and dose duration,litter considerations,some practical issues（e. g.,feasible dosing route/age/formulation/volume,blood sampling,litter considerations）,and interpretation of study results. We hope it can serve as a reference for sponsors and researchers in China when performing non-clinical safety evaluation for pediatric drugs.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2017年第2期151-161,共11页
Chinese Journal of New Drugs
