A Population Pharmacokinetics Model for Vancomycin Dosage Optimization Based on Serum Cystatin C
A Population Pharmacokinetics Model for Vancomycin Dosage Optimization Based on Serum Cystatin C
复制标题
基于血清胱抑素 C 的万古霉素剂量优化群体药代动力学模型
DOI：
10.1007/s13318-020-00621-9
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发表时间：
2020-08-01
影响因子：
1.9
通讯作者：
Liu, Tao-Tao
中科院分区：
文献类型：
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作者：
Lu, Jie-Jiu;Chen, Ming;Liu, Tao-Tao
背景与目的肾功能对万古霉素的药代动力学有重要影响，血清胱抑素C （cystatin C, CysC）作为肾功能指标具有准确的预测作用。本研究旨在建立基于儿童血清CysC的万古霉素群体药代动力学（PopPK）模型。此外，以24 h以上血药浓度-时间曲线下面积(AUC0-24)/目标范围400-700的最低抑菌浓度（MIC）比和稳态谷浓度（Css，谷）为指标，对万古霉素的剂量进行优化。方法回顾性分析2014年1月至2019年6月接受万古霉素治疗的2-18岁儿童感染患者的数据。采用非线性混合效应模型（NONMEM）软件进行PopPK分析和蒙特卡罗模拟。结果共纳入患儿220例。血清CysC和年龄是影响万古霉素药代动力学的显著协变量。间隙的最终典型值为2.25 L/h；2-7岁、7-12岁和12-18岁年龄组AUC0-24 /MIC值在400-700之间的平均概率分别为66.1%、68.1%和66.5%。2 ~ 7岁、7 ~ 12岁和12 ~ 18岁万古霉素的中、低谷值分别为7.49 ~ 11.84、5.98 ~ 11.32和5.15 ~ 11.39 mg/L， MIC为1 mg/L时，与auc0 ~ 24/MIC比值在400 ~ 700范围内高度相关。结论采用血清CysC模型估计万古霉素在儿童患者中的药动学参数。模拟剂量可为万古霉素治疗提供参考。
Background and ObjectivesRenal function has an important influence on the pharmacokinetics of vancomycin, and serum cystatin C (CysC) exhibits accurate predictive performance as a marker for renal function. This study aimed to develop a population pharmacokinetics (PopPK) model of vancomycin based on serum CysC in pediatric patients. In addition, vancomycin dosage was optimized with the area under the serum concentration–time curve over 24 h (AUC0–24)/minimum inhibitory concentration (MIC) ratio in the target range of 400–700 and the steady-state trough concentration (Css,trough).MethodsData were retrospectively obtained from pediatric patients aged 2–18 years who received vancomycin treatment for infection from January 2014 to June 2019. PopPK analysis and Monte Carlo simulations were conducted using nonlinear mixed effects model (NONMEM) software.ResultsA total of 220 children were included. Serum CysC and age were significant covariates affecting the pharmacokinetics of vancomycin. The final typical value of clearance was 2.25 L/h; the volume of distribution was 8.17 L. The average probability of target attainment values of AUC0–24/MIC ratios within 400–700 in the 2–7, 7–12, and 12–18 years age groups were 66.1%, 68.1% and 66.5%, respectively. The medianCss,troughvalues of vancomycin for the 2–7, 7–12, and 12–18 years age groups were 7.49–11.84, 5.98–11.32, and 5.15–11.39 mg/L, respectively, and were highly correlated with AUC0–24/MIC ratios in the range of 400–700 when the MIC was 1 mg/L.ConclusionsThe pharmacokinetic parameters for vancomycin in pediatric patients were estimated using a serum CysC model. The simulated dosages provide a reference for vancomycin therapy.