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精确的达普托米辛剂量:比较3-,2-,1-和0度的样本策略

Simone Giuliano¹, Manjunath P Pai², Jacopo Angelini^3,4

¹Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy.

Pharmacotherapy

|August 7, 2025

概括

一个中点采样策略提供了一种实际的方式来估计达普素暴露,提高了耐药感染的剂量准确性. 贝叶斯的双样本方法为治疗药物监测提供了最精确的结果.

科学领域:

药理动力学和药理动力学
传染性疾病传染性疾病
临床药房临床药房

背景情况:

达普托米辛是一种脂抗生素,具有狭窄的治疗窗口,需要精确的剂量.
对于耐药性阳性感染,越来越多地使用更高剂量的达普托 (8-12 mg/kg) 增加了对有效治疗药物监测 (TDM) 的需求.
优化达普素TDM策略对于平衡治疗疗效和最大限度地降低毒性至关重要.

研究的目的:

评估使用中点样本估计达普托米辛24小时曲线下的面积 (AUC24) 的精度和偏差.
为了比较中点采样策略与传统的峰值和低谷样本,以确定AUC24.
评估AUC24估计的简单计算和贝叶斯建模方法与没有TDM.

主要方法:

分析包括成人患者,至少有三个稳定状态达普素度 (峰值,中点,低谷).
使用贝叶斯估计方法 (Monolix Suite 2024R1) 采用了一个单间人群的药理动力学模型.
使用所有度 (AUCref) 估计AUC24,并使用单个或配对样本 (高峰+低谷) 重新估计;通过回归分析 (R2和平均偏差) 评估性能.

主要成果:

在210名患者中,只有45.7%的人达到目标AUC24范围 (666-939毫克·小时/升),平均AUC24为869毫克·小时/升.
一个单一的中点样本显示与AUC24 (R2=0.57) 的相关性类似于只有低谷 (R2=0.55),表现优于只有高峰 (R2=0.44).
使用高峰和低谷样本进行贝叶斯估计,获得了最高准确度 (R2=0.87) 和最低偏差.

结论:

达普托米辛的中间隔采样策略为AUC估计提供了一个切实可行的替代方案,当完全采样是不可行的.
贝叶斯的两样本方法表现出卓越的准确性,支持其更广泛的实施,用于个性化达普托米辛剂量.
优化的TDM策略对于最大限度地提高达普托米辛在治疗具有挑战性的阳性菌感染中的有效性至关重要.

关键词:

抗生素抗生素是一种抗生素.达普米辛是一种菌素.药物监测药物监测是指对药物进行监测.药物动力学药物动力学精准医学是一门精准医学.

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