Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Clinical Pharmacokinetics and Pharmacodynamics Unit, King Saud University Medical City, Riyadh, Saudi Arabia.
Antimicrob Agents Chemother. 2018 Jun 26;62(7). doi: 10.1128/AAC.00088-18. Print 2018 Jul.
The purpose of this study was to investigate the population pharmacokinetics of vancomycin in patients undergoing open heart surgery. In this observational pharmacokinetic study, multiple blood samples were drawn over a 48-h period of intravenous vancomycin in patients who were undergoing open heart surgery. Blood samples were analyzed using an Architect i4000SR immunoassay analyzer. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 168 blood samples were analyzed from 28 patients. The pharmacokinetics of vancomycin are best described by a two-compartment model with between-subject variability in clearance (CL), the volume of distribution of the central compartment (), and volume of distribution of the peripheral compartment (). The CL and the of vancomycin were related to creatinine CL (CL), body weight, and albumin concentration. Dosing simulations showed that standard dosing regimens of 1 and 1.5 g failed to achieve the PK-PD target of AUC/MIC > 400 for an MIC of 1 mg/liter, while high weight-based dosing regimens were able to achieve the PK-PD target. In summary, the administration of standard doses of 1 and 1.5 g of vancomycin two times daily provided inadequate antibiotic prophylaxis in patients undergoing open heart surgery. The same findings were obtained when 15- and 20-mg/kg doses of vancomycin were administered. Achieving the PK-PD target required higher doses (25 and 30 mg/kg) of vancomycin.
本研究旨在探讨心脏直视手术患者万古霉素的群体药代动力学。在这项观察性药代动力学研究中，对接受心脏直视手术的患者在静脉万古霉素 48 小时期间采集了多个血样。使用 Architect i4000SR 免疫分析器对血样进行分析。使用 Monolix 4.4 软件开发了群体药代动力学模型。进行了药代动力学-药效学 (PK-PD) 模拟，以探讨不同剂量方案实现药效学目标的能力。从 28 名患者中分析了总共 168 个血样。万古霉素的药代动力学最好用两室模型描述，其中清除率（CL）、中央室分布容积（）和外周室分布容积（）存在个体间变异性。万古霉素的 CL 和 与肌酐 CL（CL）、体重和白蛋白浓度有关。剂量模拟表明，1 和 1.5 g 的标准剂量方案未能达到 AUC/MIC>400 的 PK-PD 目标，MIC 为 1 mg/liter，而高体重剂量方案能够达到 PK-PD 目标。总之，标准剂量 1 和 1.5 g 万古霉素每日两次给药在接受心脏直视手术的患者中提供了不足的抗生素预防。当给予 15-和 20-mg/kg 的万古霉素剂量时，也得到了相同的发现。达到 PK-PD 目标需要更高剂量（25 和 30 mg/kg）的万古霉素。
