University Clinical Centre of the Republic of Srpska, Dvanaest beba bb, Banja Luka 78000, Bosnia and Herzegovina; Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000, Banja Luka, Bosnia and Herzegovina.
Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Beograd, Serbia.
J Crit Care. 2020 Feb;55:116-121. doi: 10.1016/j.jcrc.2019.10.012. Epub 2019 Nov 5.
The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function.
A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated.
The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL.
The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl.
本研究旨在建立包括肾功能正常和受损的成年危重症脓毒症患者在内的万古霉素群体药代动力学模型。
本研究纳入了 73 例接受 1 小时静脉输注万古霉素治疗的成年危重症脓毒症患者的 146 个浓度的前瞻性分析。采用非线性混合效应建模（NONMEM）方法进行数据分析和最终模型评估。评估了 Cockcroft-Gault 方程（CrCl）计算的肌酐清除率（CrCl）和其他潜在协变量对万古霉素清除率（CL）的影响。
最终的单室药代动力学模型包括 CrCl 对 CL 的影响。典型患者的群体药代动力学值估计为：肾功能依赖的 CL（CLCrCl）为 0.024 l/h，不依赖肾功能的 CL 残差部分为 1.93 l/h，分布容积（V）为 0.511 l/kg。根据最终模型，对于 CrCl=120 ml/min 的患者，万古霉素总 CL 的中位数为 4.81 l/h，而 CrCl 依赖部分约占 CL 的 60%。
所开发的万古霉素群体模型可用于估计成年危重症脓毒症患者的个体 CL，并可考虑 CrCl 的持续影响来个体化剂量方案。
