H-化学药物长期毒性试验技术指导原则 20070813.docVIP

精品资料 精品资料 PAGE / NUMPAGES 精品资料 指导原则编号: 【 H 】 G P T 2 - 1 化学药物长期毒性试验 技术指导原则 二○○五年三月 1 目 录 一、概述 ··························································································· 1 二、立题原则···························································································2 三、基本原则··································································································2 四、基本内容··································································································3 五、结果分析和评价···························································································7 六、结语·······················································································································10 七、参考文献················································································································10 八、附录················································································································12 九、著者·······················································································································14 2 化学药物长期毒性试验技术指导原则 一、概述 长期毒性试验（重复给药毒性试验）是药物非临床安全性评价的 核心内容，它与急性毒性、生殖毒性以及致癌性等毒理学研究有着密 切的联系，是药物从药学研究进入临床试验的重要环节。 在药物开发的过程中，长期毒性试验的目的是通过重复给药的动物 试验表征受试物的毒性作用，预测其可能对人体产生的不良反应，降低 临床试验受试者和药品上市后使用人群的用药风险。具体包括以下五个 方面：①预测受试物可能引起的临床不良反应，包括不良反应的性质、 程度、剂量－反应关系和时间－反应关系、可逆性等；②判断受试物反 复给药的毒性靶器官或靶组织；③推测临床试验的起始剂量和重复用药 的安全剂量范围；④提示临床试验中需重点监测的指标；⑤还可以为临 床试验中的解毒或解救措施提供参考。必须强调的是，长期毒性试验的 最终目的是为临床试验和临床用药服务。 本指导原则旨在为长期毒性试验提供技术参考，同时也希望能够 对药品的技术审评工作提供帮助，促进药品审评机构与药品注册申请 人之间就长期毒性试验达成更为广泛的共识。 本指导原则为化学药物长期毒性试验的一般性原则，仅代表目前 对于长期毒性试验的基本认识，其中的内容不完全是进行药物长期毒 性试验时必须完成的内容。具体药物的长期毒性试验应在本指导原则 的基础上，根据药物的自身特点制订试验方案。 1 二、立题原则 药物开发的背景和基础研究资料各不相同，在进行长期毒性试验 之前应对药物的已有资料进行综合分析，判断是否可以通过已有资料 达到长期毒性试验的目的，为临床试验和临床用药提供支持。原则上， 如果已有资料尚不能达到长期毒性试验的目的，从保证临床用药安全 的角度就应该进行长期毒性