超越作和应用:肝复合体在临床前药物安全性中的体外模型
Sushma Jadalannagari1, Lorna Ewart1
1Department of Bioinnovations, Emulate Inc, Boston, MA, USA.
Expert opinion on drug metabolism & toxicology
|March 11, 2024
概括
复杂的体外模型 (CIVMs) 显示出预测药物诱导肝损伤 (DILI) 的前景,这是药物失效的主要原因. 加快它们的采用需要进一步开发和整合计算方法,以改善临床前毒性测试.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 生物技术是生物技术.
- 药物开发 药物开发
背景情况:
- 药物诱导性肝损伤 (DILI) 是药物开发中的一个重大挑战,导致高消耗率.
- 传统的体外模型往往无法准确预测DILI,需要先进的方法.
- 复杂的体外模型 (CIVM),包括3D球体,生物打印组织和流系统,提供了增强的预测能力.
研究的目的:
- 审查目前DILI预测策略和模型的现状.
- 讨论阻碍在临床前毒性测试中广泛采用CIVM的挑战.
- 提供关于CIVM在制药研究中的未来演变和整合的前景.
主要方法:
- 用PubMed和谷歌学者进行文献搜索.
- 咨询制造商网站以获取产品信息.
- 审查了来自行业和FDA合作和战略伙伴关系的数据.
主要成果:
- 对于DILI检测,CIVM表现出良好的灵敏度和特异性.
- 尽管它们具有潜力,但制药行业对肝脏CIVM的常规采用仍然有限.
- 目前正在建立行业监管机构和开发商的合作伙伴关系,以指导CIVM的开发和资格.
结论:
- 肝脏CIVM在临床前环境中改善DILI预测具有显著的前景.
- 加快采用需要CIVM的持续演进,重点是免疫学模拟和计算集成.
- 这些进展旨在在药物开发中彻底改变DILI预测的范式.
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