数字双胞胎增强的三器官微生理系统用于研究孕妇药物药理动力学
Katja Graf1, José Martin Murrieta-Coxca2, Tobias Vogt1
1Dynamic42 GmbH, Jena, Germany.
Frontiers in pharmacology
|March 4, 2025
概括
这项研究引入了一种具有数字双胞胎的新型人类微生理系统 (MPS),以准确预测怀孕期间的药物药理动力学和胎儿暴露. 这种非动物性方法提高了对孕妇的药物安全性评估.
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
- 生殖健康 生殖健康
背景情况:
- 怀孕妇女是药物研究中的脆弱人群,原因是对药物代谢和安全性的理解有限.
- 现有的临床前模型,包括动物研究,无法充分复制人类怀孕,导致药物安全性和药理动力学的预测差距.
- 由于道德和实践的约束,孕妇制药研究受到限制.
研究的目的:
- 开发和验证一个与数字双胞胎框架集成的新型三器官微生理系统 (MPS).
- 预测怀孕期间常用药物的药理动力学和胎儿药物暴露.
- 为孕妇早期药物安全性评估提供潜在的非动物替代品.
主要方法:
- 开发了一个整合肠道,肝脏和胎盘模型的人类MPS,通过血管系统相互连接.
- 普雷尼松被用作模拟口服,新陈代谢和胎盘转移的模型化合物.
- 使用计算建模技术将MPS数据转化为人类生理学,并创建数字双胞胎.
主要成果:
- 该MPS保持了细胞完整性,并准确地模仿了体内药物动态.
- 来自该系统的预测与孕妇的临床数据密切匹配.
- 数字生与实验数据保持一致,证实了该系统在预测无毒代谢方面的价值.
结论:
- 综合MPS和数字双胞胎方法为怀孕期间的药物研究提供了一个有希望的非动物替代方案.
- 这个系统可以增强对怀孕期间药物行为和安全性的理解.
- 它支持对弱势群体的早期药物安全性评估,有可能改善孕妇及其胎儿的药物安全性.
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