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胃绕道手术后转向心血管管理:使用基于人口的分析优化卡维迪洛尔的剂量
Priscila Akemi Yamamoto1,2, Valvanera Vozmediano1, Rodrigo Cristofoletti1
1Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA.
British journal of clinical pharmacology
|June 9, 2024
概括
鲁克斯-en-Y胃绕道显著降低了卡维迪醇的生物可用性,需要更高的剂量,以获得相当的β-阻断剂效果. 个性化剂量对于RYGB患者来说至关重要,以实现治疗结果.
科学领域:
- 药理学 药理学是指药理学的学科.
- 临床药房 临床药房
- 药物新陈代谢 药物新陈代谢
背景情况:
- 鲁克斯-en-Y胃绕道 (RYGB) 改变了药物的药理动力学 (PK).
- 卡维迪醇是一种β-阻断剂,其代谢受到各种酶和输送物的影响.
- 在RYGB患者中了解卡维迪洛PK/PD对于有效治疗至关重要.
研究的目的:
- 通过基于人口的PK建模,研究RYGB对卡维迪洛PK的影响.
- 开发一个PK/PD链接模型,以优化在RYGB后患者的卡维迪洛尔剂量.
- 评估RYGB对卡维迪醇反体吸收和生物可用性的影响.
主要方法:
- 人口PK建模 (PopPK) 使用了52名受试者的数据 (非肥胖者,肥胖者,RYGB后).
- 共变量分析包括RYGB史,CYP2D6 / CYP3A4活性和肠道载体表达.
- 一个抑制的Emax PK/PD模型将 (S) - 卡维迪醇PK与运动诱导的心率变化联系起来.
主要成果:
- RYGB 减少了 50% 的卡维迪醇口服生物可用性,并延迟了吸收.
- 增加的ABCC2mRNA表达与延迟的Tmax相关.
- 在RYGB后减少 (S) - 卡维迪醇暴露 (AUC) 导致24小时β-阻断剂效应 (AUEC) 减少33%.
结论:
- 标准的卡维迪洛尔剂量对于RYGB患者来说是不够的,导致β阻塞的减少.
- 在RYGB后的患者中,每日50毫克的剂量可以达到与未经手术的25毫克患者相似的暴露和效果.
- 个性化剂量策略对于在RYGB患者服用卡维迪洛尔时实现治疗目标至关重要.
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