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基于种族和非种族方程在泰国危重症患者中用于万古霉素剂量估算的肾功能评估比较。

Comparison of Race-Based and Non-Race-Based Equations for Kidney Function Estimation in Critically Ill Thai Patients for Vancomycin Dosing.

机构信息

Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Prathom, Thailand.

出版信息

J Clin Pharmacol. 2022 Oct;62(10):1215-1226. doi: 10.1002/jcph.2070. Epub 2022 Jun 1.

Abstract

Empiric antibiotic dosing frequently relies on an estimate of kidney function based on age, serum creatinine, sex, and race (on occasion). New non-race-based estimated glomerular filtration rate (eGFR) equations have been published, but their role in supporting dosing is not known. Here, we report on a population pharmacokinetic model of vancomycin that serves as a useful probe substrate of eGFR in critically ill Thai patients. Data were obtained from medical records during a 10-year period. A nonlinear mixed-effects modeling approach was conducted to estimate vancomycin parameters. Data from 208 critically ill patients (58.2% men and 36.0% septic shock) with 398 vancomycin concentrations were collected. Twenty-three covariates including 12 kidney function estimates were tested and ranked on the basis of the model performance. The median (min, max) age, weight, and serum creatinine was 69 (18, 97) years, 60.0 (27, 120) kg, and 1.53 (0.18, 7.15) mg/dL, respectively. The best base model was a 1-compartment linear elimination with zero-order input and proportional error model. A Thai-specific eGFR equation not indexed to body surface area model best predicted vancomycin clearance (CL). The typical value for volume of distribution and CL was 67.5 L and 1.22 L/h, respectively. A loading dose of 2000 mg followed by maintenance dose regimens based on eGFR is suggested. The Thai GFR not indexed to BSA model best predicts vancomycin CL and dosing in the critically ill Thai population. A 5% to 10% absolute gain in the vancomycin probability of target attainment is expected with the use of this population-specific eGFR equation.

摘要

经验性抗生素剂量通常依赖于基于年龄、血清肌酐、性别和种族(有时)的肾功能估计。已经发表了新的非种族估算肾小球滤过率(eGFR)方程,但它们在支持剂量方面的作用尚不清楚。在这里,我们报告了一个万古霉素群体药代动力学模型,该模型可作为泰国危重症患者 eGFR 的有用探测底物。数据来自 10 年期间的病历。采用非线性混合效应建模方法估算万古霉素参数。共收集了 208 例危重症患者(58.2%为男性,36.0%为感染性休克)的 398 个万古霉素浓度数据。共测试并根据模型性能对包括 12 个肾功能估计在内的 23 个协变量进行了排序。中位数(最小,最大)年龄、体重和血清肌酐分别为 69(18,97)岁、60.0(27,120)kg 和 1.53(0.18,7.15)mg/dL。最佳基础模型是具有零级输入和比例误差模型的 1 室线性消除。一个未按体表面积指数化的泰国 eGFR 方程可最佳预测万古霉素清除率(CL)。分布容积和 CL 的典型值分别为 67.5 L 和 1.22 L/h。建议使用未按体表面积指数化的泰国 GFR 模型来预测万古霉素 CL 和危重症泰国人群的剂量。使用这种人群特异性 eGFR 方程,预计万古霉素目标浓度达标概率将提高 5%至 10%。

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