现代化临床前药物开发:新方法方法论的作用
Krina Mehta1, Christian Maass2, Lourdes Cucurull-Sanchez3
1Kyowa Kirin Inc., Princeton, New Jersey 08540, United States.
新方法方法 (NAMs) 通过整合体外和体模型来改善药物开发. 这提高了临床前预测,减少了临床试验失败和动物试验.
科学领域:
- 药物开发 药物开发
- 翻译科学 翻译科学
- 计算生物学 计算生物学
背景情况:
- 超过90%的试验药物在临床开发中失败,原因是临床前临床转化不良.
- 高成本和道德问题需要更可靠的临床前工具.
研究的目的:
- 为预测性临床前研究设计提出一个整合新方法方法 (NAMs) 的结构化工作流程.
- 提高翻译准确度,减少在药物开发中对动物研究的依赖.
主要方法:
- 集成先进的体外系统,in silico机械模型和计算技术 (AI/ML).
- 开发一个代的"a priori in silico"工作流程,以指导临床前研究设计.
- 基于生理学的药物动力学建模和定量系统药理学的应用.
主要成果:
- 案例研究表明,NAM在提高翻译准确性和减少动物使用方面具有潜力.
- 机械模型提供了对药物诱导的肝损伤和瘤微环境的见解.
- 拟议的工作流可以实现体内预测和模型改进,以提高人类预测.
结论:
- 整合计算和体外NAM优化了临床前药物开发,提高了翻译精度.
- 这种范式转变得到了监管倡议的支持,比如FDA现代化法案2.0.
- NAM正在成为临床前药物开发的标准,减少临床试验失败.
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