在肥胖成年患者的初始治疗中,万科米辛的群体药理动力学和剂量建议
Lucie Polášková1, Irena Murínová1,2, Jana Gregorová3
1Department of Clinical Pharmacy, Military University Hospital Prague, Prague, Czechia.
这项研究开发了一种针对肥胖患者的范胺剂量模型,使用基于肌的eGFR和瘦体质来优化范胺清除并实现治疗目标.
科学领域:
- 药理动力学和药理动力学
- 肥胖医学 肥胖医学
- 传染病药理学 传染病药理学
背景情况:
- 在肥胖患者中服用万科米辛剂量是具有挑战性的,因为药物动力学参数发生了变化.
- 2020年共识指南推一种新的PK/PD目标 (AUC/MIC比率为400-600) 用于万科米辛治疗.
- 在这个人群中,个性化剂量对于优化万科米辛的疗效和最大限度地降低毒性至关重要.
研究的目的:
- 在成年肥胖患者中开发万科米辛的人口药理动力学 (PopPK) 模型.
- 为了确定可靠的共变量,用于万科米辛剂量个性化.
- 为了最大限度地实现推的万科米辛PK/PD目标 (AUC/MIC比率为400-600).
主要方法:
- 对138名肥胖患者 (BMI ≥30 kg/m2) 治疗药物监测数据的分析.
- 非线性混合效应建模,以开发PopPK模型.
- 蒙特卡洛模拟以确定最佳的剂量策略,以实现目标.
主要成果:
- 建立了一种PopPK模型,其中菌素清除率 (CL) 与估计的淋巴细胞过率 (eGFR) 和瘦体质量正相关.
- 基于肌素的eGFR比基于囊素的eGFR更好地预测了万科米辛CL.
- 人口中位数估计:Vd = 74.0 L,CL = 6.65 L/h,半衰期 = 7.7 小时.
结论:
- 基于共变的万科米辛剂量个性化,特别是使用基于肌素的eGFR,可以优化肥胖患者的PK/PD目标实现.
- 专注于个性化剂量的临床药房干预可以改善万科米辛治疗结果.
- 这种方法支持通过达到推的AUC/MIC比率来最大限度地提高万科米辛的疗效.
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