Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
J Pharmacokinet Pharmacodyn. 2019 Jun;46(3):251-261. doi: 10.1007/s10928-019-09633-8. Epub 2019 Apr 8.
This study aimed to characterize the population pharmacokinetics (PKs) of piperacillin and investigate probability of target attainment (PTA) and cumulative fraction of response (CFR) of various dosage regimens in critically ill patients during the early phase of sepsis. Forty-eight patients treated with piperacillin/tazobactam were recruited. Five blood samples were drawn before and during 0-0.5, 0.5-2, 2-4 and 4-6 or 8 h after administration. Population PKs was analyzed using NONMEM. The PTA of 90%fT target and CFR were determined by Monte Carlo simulation. The two compartment model best described the data. Piperacillin clearance (CL) was 5.37 L/h, central volume of distribution (V) was 9.35 L, and peripheral volume of distribution was 7.77 L. Creatinine clearance (CL) and mean arterial pressure had a significant effect on CL while adjusted body weight had a significant impact on V. Subtherapeutic concentrations can occur during the early phase of sepsis in critically ill patients with normal renal function. The usual dosage regimen, 4 g of piperacillin infused over 0.5 h every 6 h, could not achieve the target for susceptible organisms with MIC 16 mg/L in patients with CL ≥ 60 mL/min. Our proposed regimen for the patients with CL 60-120 mL/min was an extended 2 h infusion of 4 g of piperacillin every 6 h. Most regimens provided CFR ≥ 90% for the E. coli infection while there was no dosage regimen achieved a CFR of 90% for the P. aeruginosa infection.
这项研究旨在描述哌拉西林的群体药代动力学（PKs），并研究脓毒症早期危重症患者各种剂量方案的目标浓度达标概率（PTA）和累积反应分数（CFR）。共招募了 48 名接受哌拉西林/他唑巴坦治疗的患者。在给药前和给药后 0-0.5、0.5-2、2-4 和 4-6 或 8 h 时采集了 5 份血样。使用 NONMEM 分析群体 PKs。通过蒙特卡罗模拟确定 90%fT 目标的 PTA 和 CFR。两室模型最能描述数据。哌拉西林清除率（CL）为 5.37 L/h，中央分布容积（V）为 9.35 L，外周分布容积为 7.77 L。肌酐清除率（CL）和平均动脉压对 CL 有显著影响，调整后的体重对 V 有显著影响。在肾功能正常的危重症脓毒症患者中，早期可能会出现治疗浓度。通常的剂量方案，即每 6 小时输注 4 g 哌拉西林 0.5 小时，对于 CL ≥ 60 mL/min 的患者，MIC 为 16 mg/L 的敏感菌可能无法达到目标。我们提出的 CL 为 60-120 mL/min 的患者的方案是每 6 小时延长 2 小时输注 4 g 哌拉西林。大多数方案为大肠杆菌感染提供了 CFR≥90%，但没有一种方案能使铜绿假单胞菌感染的 CFR 达到 90%。
