化学药物急性毒性研究技术指导原则.pdf

指导原则编号: 【 H 】 G P T 1 - 1



化学药物急性毒性研究技术指导原则
(第二稿)
















二 OO 四年三月一日
急性毒性研究技术指导原则


目录
一、概述····························································································2
二、基本原则····························································································3
三、研究内容····························································································3
四、数据分析及评价····························································································5
五、名词解释····························································································6
六、参考文献····························································································6
七、附录····························································································7
八、起草说明····························································································17
九、著者····························································································20
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急性毒性研究技术指导原则
一、概述
动物急性毒性试验是指动物一次或 24 小时内多次给予受试物后,一定时间
内所产生的毒性反应。
所有拟用于人的药物通常需要进行动物急性毒性试验[1]。从新药开发的客观
规律来看,急性毒性试验处在毒理研究的早期阶段,所获得的信息有助于重复
给药毒性试验的剂量选择,初步揭示受试物可能的毒性作用靶器官,同时也会
暴露一些迟发的毒性反应。另外,急性毒性试验的结果有时可用作Ⅰ期临床试
验起始剂量选择的参考,并能提供一些与人类急性药物中毒相关的信息[1,2]。
anization of Economic Corporation and Development)于 1987
提出的动物急性毒性试验称为经典的急性毒性试验[3],为新药的开发作出了重要
贡献。美国、欧盟、日本为了国际注册要求的统一协调,于 1991 年召开了第一
次人用药品注册技术要求国际协调会(ICH1),对经典急性毒性试验进行了科
学、客观的分析与评价,认为经典急性毒性试验存在较大的局限性,有些要求
缺乏科学基础。各方在科学的基础上就急性毒性试验达成了共识:建议采用两
种啮齿类动物或一种啮齿类动物加一种非啮齿类动物的严格设计的、单次给药
的、逐渐增加剂量的耐受性研究,取代啮齿类动物或非啮齿类动物半数致死量
[4]
(LD50)测定的要求。在 1997 年进行的第二次ICH会议中,又对支持单次给
药临床试验的动物急性毒性试验进行了讨论[5]。
我国在 1993 年和 2001 年分别发布了两版有关急性毒性试验的指导原则,
在我国的新药研发中发挥了重要作用。随着我国加入 WTO,国产新药进行国际
注册成为必然,这种情况下,技术指导原则应首先符合国际注册的要求。此次
制定本指导原则的目的是,在我国原指导原则的基础上,结合我国科研实践的
经验和具体情况,参考 ICH 框架下三方各国的指导原则,制定出既符合我国国
情又符合国际注册要求的动物急性毒性研究技术指导原则。
本技术指导原则适用于化学药品的动物急性毒性研究。
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本指导原则重点阐述急性毒性试验中动物、剂量、