在器官缺陷研究中使用基于人口药理动学的虚拟控制组的可行性
Islam R Younis1, Fan Wang2, Ahmed A Othman1
1Gilead Sciences, Inc., Foster City, CA, USA.
Journal of clinical pharmacology
|February 12, 2024
概括
人口药理动力学 (popPK) 可以为器官功能障碍研究创建虚拟健康对照组. 这种方法与观察到的数据有很好的一致性,支持其在未来的研究中使用.
科学领域:
- 药理动力学和药物新陈代谢
- 临床药理学 临床药理学
- 生物统计学 生物统计学
背景情况:
- 器官功能障碍研究通常需要健康的对照组进行比较.
- 招募和管理健康的控制可以是资源密集的.
- 种群药动力学 (popPK) 建模为生成虚拟对照组提供了一个潜在的替代方案.
研究的目的:
- 评估使用popPK生成虚拟健康对照组用于器官功能障碍研究的可行性.
- 评估模拟和观察的药理动力学参数 (AUC,Cmax) 之间的一致性.
主要方法:
- 分析了来自7种药物11项器官功能障碍研究的数据.
- 每项研究对1000名虚拟健康对照进行了模拟的个人度-时间概况.
- 用AUC和Cmax计算的几何平均比率 (GMR) 来比较模拟和观察的暴露.
主要成果:
- 在73%的研究中,模拟健康对照暴露在观察暴露的30%以内.
- 基于模拟的AUC和Cmax的GMR分别在72%和83%的手臂中处于观察到的GMR的90%置信区间内.
- 在一个药物中观察到不良一致性,而健康参与者的数据被排除在popPK模型之外.
结论:
- 基于PopPK的虚拟控制组是可行的,并支持在器官功能障碍研究中使用它们.
- 需要进一步的研究,以建立构建这些虚拟控制组的最佳实践.
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