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注意差距:基于模型的切换从塞拉托格林到口服P2Y12受体对抗剂的维持疗法
Chih-Hsuan Hsin1, Jasper Dingemanse1, Andrea Henrich1
1Department of Clinical Pharmacology, Idorsia Pharmaceuticals Ltd., 4123 Allschwil, Switzerland.
Biomolecules
|September 28, 2023
概括
快速作用的P2Y12抑制剂塞拉托格雷尔可以切换为口服抗血小板治疗. 药理动力学/药理动力学建模指导了急性心肌梗塞后从西拉托格勒向口服P2Y12抗剂的安全过渡.
科学领域:
- 药理学和治疗学 药理学和治疗学
- 心血管医学 心血管医学
- 临床药理学 临床药理学
背景情况:
- 塞拉托格雷尔是一种新型P2Y12受体对抗剂,旨在在急性心肌梗塞 (AMI) 期间进行皮下自我注射.
- 它的快速,强效和短效的特征旨在减轻AMI症状发作和医疗干预之间的时间差距.
- 之前的研究表明,西拉托格勒与口服P2Y12充满剂量之间存在药学动力学相互作用,因此需要对治疗转换进行研究.
研究的目的:
- 为了预测血小板聚合 (IPA) 的抑制,从西拉托格勒转向口服P2Y12抗剂.
- 为临床实践提供基于模型的指导,关于切换抗血小板疗法.
- 支持急性心肌梗塞患者的安全有效管理.
主要方法:
- 使用了人口药理动力学/药理动力学 (Pop-PK/PD) 建模和模拟.
- 场景包括西拉托格勒或安慰剂,其次是克洛皮多格勒加重剂量,然后是普拉苏格勒或提卡格勒维护剂量.
- 随着时间的推移,在各种模拟治疗过渡时间中,量化估计了IPA水平.
主要成果:
- 使用提卡格勒或普拉苏格勒的维护疗法在用克洛皮多格勒加重剂量后迅速达到持续的IPA水平>80%.
- 一个特定的窗口 (18-24小时后selatogrel) 显示,如果克洛皮多格勒被给予12小时后selatogrel.
- 塞拉托格雷尔维持了比安慰剂更高的IPA,当克洛皮多格雷尔12小时后被施用时,在维护前下降之前,在16小时内保持了比安慰剂更高的IPA.
结论:
- 基于模型的预测成功地告知了从皮下血红到口服P2Y12抑制剂治疗的过渡策略.
- 药理动力学和药理动力学建模在模拟复杂的抗血小板治疗切换场景方面表现出价值.
- 这些发现支持制定临床指导方针来管理需要顺序P2Y12抑制的患者.
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