帕尔博西基布与里瓦罗克萨班或阿皮克萨班之间的体内药理学相互作用:增加药物暴露和剂量调整的影响
在PubMed上查看摘要
概括
此摘要是机器生成的。通过影响它们的吸收和清除,Palbociclib显著增加了对apixaban和rivaroxaban的暴露. 在老鼠中观察到的这种相互作用表明,在联合使用时可能需要调整剂量.
科学领域
- 药理学
- 药物相互作用
- 毒理学
背景情况
- 艾皮克萨班和里瓦罗克萨班是口服的直接XA抑制剂.
- 作为CDK4/ 6抑制剂的Palbociclib可能会改变这些抗凝剂的药理学.
- 这种药物相互作用的确切机制尚未完全理解.
研究的目的
- 在大鼠模型中评估palbociclib对apixaban和rivaroxaban的药理学影响.
- 阐明这些药物相互作用的机制.
- 根据药物组合使用的最佳剂量方案.
主要方法
- 雄性Sprague- Dawley大鼠接受了单剂或联合剂量的palbociclib与apixaban或rivaroxaban.
- 使用UPLC-MS/MS测量了血药物度.
- 对CYP3A4,P- 糖蛋白和BCRP的mRNA表达进行了分析,以了解相互作用机制.
主要成果
- 帕尔博西基布显著增加了阿皮克萨班暴露 (AUC,Cmax) ~2倍,而里瓦罗克萨班增加了~4倍.
- 同时使用降低了两种抗凝剂的清除量和分布量.
- 即使在降低剂量时,药物暴露仍然很高,但在12小时间隔服用时,情况并非如此.
结论
- 帕尔博西基布增强了阿皮克萨班和里瓦罗克萨班的肠道吸收,可能是通过降低P-gp和BCRP的表达.
- 这些发现表明生物可用性改善和毒性改变的可能性.
- 优化组合剂量方案对于安全有效的同时使用至关重要.
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