尼莫迪平的剂量和药理动力学变异性在脑下关节下出血患者
Judith Bellapart1, María Patricia Hernández-Mitre2, Xiaolin Wu2
1Royal Brisbane and Women's Hospital, Australia.
概括
尼莫迪平用于下关节出血,具有可变的生物可用性和最小的脑脊液透. 诸如年龄,食物摄入量和服用途径等因素会影响其有效性,这表明需要优化剂量策略.
科学领域:
- 药理学 药理学是指药理学的学科.
- 神经科学是一个神经科学.
- 临床药房 临床药房
背景情况:
- 尼莫迪平是延迟大脑缺血症 (DCI) 的唯一预防方法,该疗法是在动脉瘤下关节出血 (SAH) 后进行的.
- 目前固定剂量尼莫迪平的使用忽略了影响DCI治疗疗效的患者特异性因素.
- 了解尼莫迪平的药理动力学对于制定个性化剂量策略至关重要.
研究的目的:
- 在SAH患者中描述肠道尼莫迪平的血和脑脊液 (CSF) 药理动力学.
- 为了研究施用途径和养状态对尼莫迪平生物可用性的影响.
- 为了确定影响尼莫迪平药物动力学的患者特异性因素.
主要方法:
- 在接受尼莫迪平的SAH患者的连续血和CSF采样.
- 使用超高性能液体染色学-并联质谱法量化尼莫迪平度的量化.
- 通过非分区和非线性混合效应建模进行药理动力学分析,评估路径和养状态的影响.
主要成果:
- 一个两部分人群的药理动力学模型确定了年龄作为清除的重要共变量.
- 中位数CSF-to-plasma nimodipine暴露率为0.35%,表明CSF透率最小且高度可变.
- 摄入食物显著降低了尼莫迪平的生物可用性,影响了口服和鼻胃管理.
结论:
- 鼻胃给药和非禁食条件可能会降低尼莫迪平的生物可用性.
- 尼莫迪平在CSF中具有最小且可变的透率.
- 年龄是尼莫迪平清除的一个关键决定因素,需要优化给药和进一步研究最佳剂量.
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