尼马特里尔维尔/里托纳维尔的剂量建议使用综合人群药理动力学分析
Phylinda L S Chan1, Ravi Shankar P Singh2, Donna S Cox3
1Worldwide Research, Development and Medical, Pfizer R&D UK Ltd., Sandwich, Kent, UK.
CPT: pharmacometrics & systems pharmacology
|October 7, 2023
概括
与利托纳维尔 (PAXLOVID) 联合使用的尼尔马特雷尔维尔的药理学分析了患有和没有COVID-19的成年人. 分析支持目前用于正常功能的剂量,并指导适度功能障碍和儿科的调整.
科学领域:
- 药理动力学和药物新陈代谢
- 传染病和病毒学 传染病和病毒学
- 临床药理学 临床药理学
背景情况:
- 与利托纳维尔 (PAXLOVIDTM) 联合使用的尼尔马特雷尔维尔是一种口服生物可用抗病毒,用于治疗轻度至中度的COVID-19.
- 了解尼马特里尔维尔的药理动力学对于优化治疗和确保安全至关重要.
- 包括COVID-19患者在内的不同人群的先前药理动力学数据需要全面分析.
研究的目的:
- 在成年人中与里托纳维尔联合使用时,描述nirmatrelvir的群体药理动力学.
- 为了评估共变量的影响,如COVID-19,功能,年龄和药物相互作用对nirmatrelvir的药理动力学.
- 支持和完善对不同成人和儿科患者群体的涅马特里尔维尔/里托纳维尔的剂量建议.
主要方法:
- 使用来自八项已完成的I期和II/III期研究的聚合血尼马特里尔维尔度的群体药理动力学分析.
- 使用逐步前进选择和倒退消除方法检查的共变量影响.
- 与5000名受试者进行模拟,以支持剂量建议和指导剂量调整.
主要成果:
- 开发了一种具有第一阶吸收,体重全度量缩放和剂量依赖吸收的两部分模型.
- 涅马特里尔维尔清除受功能 (nCLCR),药物相互作用,COVID-19状态,配方和年龄的影响.
- 模拟结果支持目前的剂量为300/100毫克每天两次,用于正常/轻度功能障碍和特定儿科组,以及150/100毫克每天两次,用于中度功能障碍.
结论:
- 种群的药理动力学模型准确地描述了当与利托纳维尔联合使用时的nirmatrelvir行为.
- 该分析为当前的剂量建议提供了基础,并确定了剂量调整的关键因素.
- 这些发现支持在成人和儿科中使用尼马特里尔维尔/里托纳维尔,并对功能障碍进行适当的剂量修改.
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