Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
University of Ulsan College of Medicine, Seoul, Korea.
Clin Exp Pharmacol Physiol. 2022 Feb;49(2):202-211. doi: 10.1111/1440-1681.13597. Epub 2021 Oct 23.
The aim of this prospective study was to construct a new pharmacokinetic model of vancomycin for target-concentration controlled infusion (TCI). As the first loading dose, 25 mg/kg of vancomycin was administered during 60-90 min. Arterial blood samples were obtained at pre-set intervals to measure the serum concentrations of vancomycin. Population pharmacokinetic analysis was performed using the NONMEM software (ICON Development Solutions). In total, 197 serum concentration measurements from 22 patients were used to characterise the pharmacokinetics of vancomycin. A three-compartment mammillary model best described the pharmacokinetics of vancomycin in critically ill patients. The ideal body weight was a significant covariate for the central and slow peripheral volume of distribution. The weight and age converted to categorical variables at a cut-off of 65 years were a significant covariate for the clearance. Based on the results of stochastic simulation, the TCI method maintained the therapeutic concentration range for the longest duration. In addition, assuming that vancomycin was administered by the TCI method for 7 days, the dose was reduced by about 15% compared with the standard administration methods. The daily area under the curve values were maintained between 500 mg·h/L and 600 mg·h/L. TCI has the potential to become a new infusion method for patient-tailored dosing in critically ill patients. To administer vancomycin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.
本前瞻性研究旨在构建万古霉素的新型药代动力学模型，以实现目标浓度控制输注（TCI）。首剂给予 25mg/kg 万古霉素，输注时间 60-90 分钟。设定时间间隔采集动脉血样以测定万古霉素的血清浓度。采用 NONMEM 软件（ICON Development Solutions）进行群体药代动力学分析。共纳入 22 例患者的 197 个血清浓度测量值，用于描述万古霉素的药代动力学特征。三房室乳突模型可最好地描述重症患者万古霉素的药代动力学。理想体重是中央和缓慢外周分布容积的重要协变量。体重和年龄经转换为 65 岁的分类变量是清除率的重要协变量。基于随机模拟结果，TCI 方法可维持最长时间的治疗浓度范围。此外，假设万古霉素通过 TCI 方法输注 7 天，与标准给药方法相比，剂量减少约 15%。每日曲线下面积值维持在 500mg·h/L 至 600mg·h/L 之间。TCI 有可能成为重症患者个体化给药的新输注方法。为了在临床实践中通过 TCI 给予万古霉素，应进行新构建的药代动力学模型的适当外部验证。
