化学药物长期毒性试验技术指导原则

《化学药物长期毒性试验技术指导原则》由会员上传分享，免费在线阅读，更多相关内容在行业资料-天天文库。

1、指导原则编号:【H】GPT2-1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、······································································2四、基本内容··································································································3五、结果分析和评价·····················································································

3、······7六、结语·······················································································································10七、参考文献················································································································10八、附录··············

4、··································································································12九、著者·······················································································································142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

5、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

6、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

7、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试验；反之，则可以不必进行长期毒性试验。三、基本原则（一）试验管理根据《中华人民共和国药品管理法》的规定，药物的长期毒性试验必须执行《药物非临床研究质量管理规范》。（二）整体性药物的开发是一个连续的、渐进的系统工程，长期毒性试验是药物开发的一个有机组成部分。长期毒性试验不能与药效学、药代动力学和其他毒理学研究割裂，试验设计

8、应充分考虑其他药理毒理研究的试验设计和研究结果。长期毒性试验的结果应该力求与其他药理毒理试验结果互为印证、说明和补充。（三）具体问题具体分析长期毒性试验的试验设计应该在对受试物的认知基础上，遵循“具体问题具体分析”的原则