艾米卡辛在急诊室的剂量优化:一个人口药理动力学模拟研究
Nada Dia1, Sabrina De Winter2, Matthias Gijsen1,2
1Department of Pharmaceutical and Pharmacological Sciences, KU Leuven.
Therapeutic drug monitoring
|May 9, 2025
概括
在败血症中标准的阿米卡辛剂量是不够的. 单一的1500mg剂量可以确保有效性,但在更高的细菌敏感度水平下,为了安全需要更高的剂量.
科学领域:
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
- 临床药房 临床药房
背景情况:
- 成年败血症患者接受15毫克/公斤IV阿米卡辛的治疗显示目标的达到不足.
- 这种不足在2 mg/L的局部最小抑制度 (MIC) 和欧洲抗菌感应性测试委员会 (EUCAST) 肠道细菌的8 mg/L的断点下观察到.
研究的目的:
- 确定阿米卡辛的剂量策略,在所有成人败血症患者中实现临床上可接受的目标实现概率 (PTA).
- 为了优化阿米卡辛的剂量,在重症患者中提高疗效和安全性.
主要方法:
- 使用NONMEM 7.5进行人口药理动力学建模,采用两部分模型.
- 随机模拟评估了不同患者特征 (体重,BMI,通过eGFR CKD-EPI通过功能) 的各种剂量策略.
- 药理动力学-药理动力学目标包括AUC24/MIC≥80的疗效和C24h<3 mg/L的安全性在MIC的2 mg/L和8 mg/L.
主要成果:
- 在8mg/L断点时,标准15mg/kg剂量达到<90%PTA.
- 一个平坦的1500毫克剂量达到≥90%的PTA在2毫克/升MIC的整个人口.
- 在8mg/L断点时,仅在EGFRCKD-EPI<96mL/min/1.73m2的患者中,达到≥90%的PTA的平坦3500mg剂量.
- 与1500 mg和15 mg/kg剂量相比,3500 mg的剂量导致更高的C24h.
结论:
- 在败血症中,偏好平坦剂量,而不是基于体重的阿米卡辛剂量.
- 1500毫克的剂量可能会在较高的MIC (8毫克/升) 中危及安全,而3500毫克的剂量可能会在较低的MIC (2毫克/升) 中危及疗效.
- 建议剂量策略的临床验证是必要的.
相关概念视频
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01:25Clearance Models: Compartment Models
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01:26Pharmacokinetic Models: Comparison and Selection Criterion
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