功能作为高剂量L-carnitine在败血症休克中药理学反应的关键驱动因素
Theodore S Jennaro1, Michael A Puskarich2,3, Thomas L Flott1
1Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
高剂量的勒沃卡尼丁 (L-卡尼丁) 在败血症休克中的药理动力学最好用一个两模型来描述. 使用cystatin C改善模型匹配的功能估计,建议对功能进行剂量调整至关重要.
科学领域:
- 药理动力学和药理动力学
- 关键护理医学 关键护理医学
- 腎臟病學 (nephrology) 是一種醫學.
背景情况:
- 败血栓休克的死亡率很高 (接近40%).
- 利沃卡尼丁 (L-卡尼丁) 在败血症休克中显示出治疗潜力.
- 高剂量静脉注射L-卡尼丁补充剂产生可变的血清度.
研究的目的:
- 描述高剂量L-卡尼丁在败血症休克中的群体药理动力学 (PK).
- 在PK模型中评估各种功能估计值作为共变量.
- 评估PK参数,治疗前代谢物和药物反应之间的相关性.
主要方法:
- 使用非线性混合效应模型 (Monolix) 进行人口PK分析.
- 从第二阶段L-卡尼丁试验中获取血清样本和代谢学数据.
- 测试功能估计 (eGFR,CKD-EPI,Cockcroft-Gault) 和其他共变量.
主要成果:
- 一个具有线性淘汰的两部分模型最好地描述了L-carnitine PK.
- 功能估计,特别是使用CKD-EPI (肌素和囊素C) 的eGFR,显著改善了模型的合适性.
- 这种eGFR方程表现优于较旧的方程和肌素清除.
结论:
- 高剂量的L-卡尼PK在败血症休克中是通过两模型的良好特征.
- 使用cystatin C估计功能提供了卓越的模型准确性.
- 未来的剂量策略应考虑功能和基线代谢状态.
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