在患有侵袭性 кандидоз症的重症患者中,安尼杜拉金的暴露和人群药理动力学
Omar Elkayal1, Yannick Hoffert1, Beatrijs Mertens1,2
1Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Infection
|December 6, 2024
概括
标准的anidulafungin剂量对于患有侵入性Candida感染的重症患者来说是不够的. 这项研究发现非最佳的药理动力学-药理动力学目标实现,突出了个性化剂量策略的需要.
科学领域:
- 药理学 药理学是指药理学的学科.
- 临界护理医学 临界护理医学
- 传染性疾病 传染性疾病
背景情况:
- 安尼杜拉金是侵袭性坎迪达菌感染的第一线治疗方法.
- 危急病患者表现出显著的药物动力学变异性,可能会影响治疗疗效.
- 标准剂量可能无法确保在这个人群中达到足够的药理动力学-药理动力学 (PKPD) 目标.
研究的目的:
- 评估在重症患者中对anidulafungin的暴露和PKPD目标的实现.
- 在这个患者群体中开发一种对anidulafungin的种群药动力学 (popPK) 模型.
- 评价患者特异性因素对实现阿尼杜拉金PKPD目标的影响.
主要方法:
- 纳入了接受标准anidulafungin剂量的成年ICU患者.
- 富血采样是在治疗的早期和晚期进行的.
- 开发了一种两部分的popPK模型,并进行蒙特卡洛模拟来评估目标的实现 (AUC24h目标为83.5 mg×h/L).
主要成果:
- 在PKPD的第2天达到45%,第5天达到65%.
- 抗素清除率随体重增加而增加;分布量随血清白蛋白降低而增加.
- 体重和血清白蛋白显著影响了PKPD目标的实现,特别是在第1天和第14天.
结论:
- 标准的anidulafungin剂量不足以在重症患者中达到足够的暴露.
- 为了优化治疗结果,需要个性化剂量策略.
- 有一个交互式模拟工具可用于支持剂量查找研究.
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