使用基于总和未结合度的人口方法,为重症儿童制定量身定制的西普洛克萨剂量建议
Pieter-Jan De Sutter1, Evelyn Dhont2, Daphné Vens3
1Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Belgium.
标准的西普洛克萨辛剂量对于重症儿童来说是不够的,尤其是那些不接受机械呼吸的儿童. 优化剂量对于实现治疗目标和改善儿童重症监护的患者结果至关重要.
科学领域:
- 药理动力学和药理动力学
- 儿童重症监护医疗
- 传染病药物治疗
背景情况:
- 由于药物适应性发生变化,对重症儿童的最佳剂量是具有挑战性的.
- 了解药物暴露的个体间差异对于有效治疗至关重要.
研究的目的:
- 在重症儿童中开发一种人群药理学 (PK) 模型.
- 确定PK变异的预测因素,并评估目标的实现.
- 为量身定制的治疗提供基于证据的剂量建议.
主要方法:
- 在44名重症儿童中进行前性,开放式,多中心的瘤学研究.
- 静脉注射西普罗夫洛克萨辛,并进行血尿采样.
- 分析总和未结合药物度的群体PK建模.
主要成果:
- 通过二分隔模型描述的西普罗素PK.
- 清除受膜过率和机械通风的影响.
- 标准剂量达到0. 25 mg/ L的低于最佳目标水平 (75- 80%).
- 达到适当的目标 (≥90%) 需要10 mg/ kg每12小时 (透气) 或15 mg/ kg每8小时 (非透气,正常的功能).
结论:
- 标准的西普罗夫洛克萨辛剂量 (20 - 30毫克/ 千克/ 天) 不适用于正常/ 升高功能的非通风的重症儿童.
- 要达到治疗目标,需要强化剂量方案.
- 进一步的研究应评估高剂量西普洛的有效性和安全性.
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