对capivasertib和CYP3A4基质米达佐拉姆在患有晚期固体瘤的患者中的药理动力学研究
Claire Miller1, Roberto Sommavilla2, Cindy L O'Bryant3
1Clinical Pharmacology and Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
卡比瓦塞尔蒂布是一种弱CYP3A抑制剂,显示米达佐拉姆暴露增加1.75倍. 这种AKT抑制剂在晚期固体瘤患者中耐受性良好,显示出临床活性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
- 药物相互作用 药物相互作用
背景情况:
- 卡皮瓦塞尔蒂布是一种AKT激酶抑制剂,在晚期癌症中进行评估.
- 了解药物相互作用对于安全的癌症治疗至关重要.
研究的目的:
- 为了评估capivasertib和CYP3A基质米达佐拉姆之间的药物相互作用风险.
- 为了评估capivasertib作为CYP3A抑制剂的潜力.
主要方法:
- 晚期固体瘤的成年患者接受了capivasertib (400 mg两日间歇性方案) 和米达佐拉姆 (1 mg).
- 在周期1的第1,8和12天分析了米达佐拉姆的药理动力学.
- 评估了安全性和探索性疗效.
主要成果:
- 同时使用会增加米达佐拉姆的暴露,AUCinf和Cmax比分别高达1.75和1.25.
- 卡皮瓦塞尔蒂布 (Capivasertib) 显示出可管理的安全性.
- 两名患者实现了部分反应.
结论:
- 在研究的剂量和时间表下,capivasertib作为弱CYP3A抑制剂起作用.
- 卡皮瓦塞尔蒂布耐受性良好,并且在重度预先治疗的患者中显示出初步的临床活性.
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