在患有晚期或转移性固体瘤的患者中,capivasertib的人口药理动力学
Carlos Fernandez-Teruel1, Marie Cullberg2, Cath Eberlein3
1Clinical Pharmacology and Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
这项研究开发了capivasertib,一个泛-AKT抑制剂的人口药理动力学模型. 大多数患者因素并没有显著影响capivasertib的药理动力学,这表明没有必要调整剂量.
科学领域:
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
- 临床药理学 临床药理学
背景情况:
- 在各种癌症中,PI3K/AKT通路经常过度激活.
- 卡皮瓦塞尔蒂布是一种强效和选择性抑制剂,向全AKT通路.
研究的目的:
- 为 capivasertib.开发一个人群药理动力学 (PK) 模型.
- 评估内在和外在因素对capivasertib PK的影响.
主要方法:
- 来自四项I/II期研究的综合药理动力学数据.
- 评估的共变量包括剂量,时间表,患者人口统计,器官功能和同时服用的药物.
- 使用一个三模型来描述头垂直处置.
主要成果:
- 卡皮瓦塞尔提布PK显示中度的时间和剂量依赖的清除.
- 体重,同时服用帕克利塔塞尔,食物效果和配方显著影响了PK,但效果小于20%.
- 大多数评估的共同变量,包括年龄,性别,种族和/肝功能,并没有显著影响capivasertib PK.
结论:
- 卡皮瓦塞尔提布PK表现出对象之间适度的变化.
- 确定的因素,如体重和帕克利塔克塞尔的同时使用,在统计学上显著,但对暴露的影响很小.
- 根据这一群体PK分析,对于内在和外在因素不需要先验剂量调整.
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