药物诱导性肝损伤 (DILI) 的新方法方法 (NAM):我们现在在哪里?
Shivangi Shrimali1, Minjun Chen1, Dongying Li1
1National Center for Toxicological Research, U.S. Food and Drug Administration (FDA), 3900 NCTR Road, Jefferson, AR 72079, USA.
Drug discovery today
|August 13, 2025
概括
这项研究评估了用于预测药物诱导性肝损伤 (DILI) 的新方法方法 (NAM). 虽然体外NAM显示出希望,但对于可靠的DILI预测,需要一个标准化的参考列表.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 生物医学工程 生物医学工程
- 监管科学 监管科学
背景情况:
- 美国食品和药物管理局 (FDA) 推动新方法方法 (NAMs) 以减少在临床前安全性中对动物进行试验.
- 药物诱导性肝损伤 (DILI) 仍然是药物开发中的一个重大安全问题.
- 目前用于DILI预测的方法包括动物研究和新兴的体外技术.
研究的目的:
- 为了比较体外NAM,动物研究和微生理系统 (MPS) 对DILI的预测性能.
- 确定在监管科学中推进NAM的挑战和机会.
- 提出一个资源,用于对DILI预测NAM的系统评估.
主要方法:
- 文献综述,重点关注重叠药物及其DILI结果.
- 在体外NAM,动物模型和MPS数据的比较分析.
- 从现有文献中编制一个精心策划的参考药物清单.
主要成果:
- 在不同的体外NAM中观察到相当大的变化.
- 实验室内NAM证明了对DILI预测的传统动物模型的潜在优势.
- 对微生理系统 (MPS) 的有限数据阻止了全面的比较.
- 为了帮助NAM开发,编制了一份参考药物清单DILIference.
结论:
- 标准化的方法和参考数据集对于验证DILI预测NAM至关重要.
- 拟议的DILI引用列表可以指导NAM的开发和基准测试.
- 需要进一步的研究来提高DILI评估NAM的可靠性和监管接受度.
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