Niibe Yoko, Suzuki Tatsuya, Yamazaki Shingo, Suzuki Takaaki, Takahashi Nozomi, Hattori Noriyuki, Nakada Taka-Aki, Oda Shigeto, Ishii Itsuko
Division of Pharmacy, University Hospital.
Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Chiba University; and.
Ther Drug Monit. 2020 Aug;42(4):588-594. doi: 10.1097/FTD.0000000000000741.
The aim of this study was to conduct a population pharmacokinetic (PK) analysis of meropenem and to explore the optimal dosing strategy for meropenem in critically ill patients with acute kidney injury receiving treatment with continuous hemodiafiltration (CHDF).
Blood samples were obtained on days 1, 2, and 5 after the start of meropenem administration, immediately before dosing, and at 1, 2, 6, and 8 hours after dosing. Population PK model analysis was performed and concentration-time profiles were simulated using the Nonlinear Mixed Effects Model software.
Twenty-one patients receiving CHDF in our intensive care unit were enrolled and 350 serum concentration-time data points were obtained. The PKs of meropenem were best described using a 2-compartment model. Typical total and intercompartmental clearance values were 4.22 L/h and 7.84 L/h, respectively, whereas the central and peripheral compartment volumes of distribution were 14.82 L and 11.75 L, respectively. Estimated glomerular filtration rate was identified as a significant covariate of meropenem total clearance. In simulations of patients with renal failure receiving CHDF, the dose was affected by estimated glomerular filtration rate; a dose of 0.5 g every 8 hours or 1 g every 12 hours showed the probability of target attainment of achieving 100% time above the minimum inhibitory concentration for bacteria with a minimum inhibitory concentration ≤2 mg/L.
A population PK model was developed for meropenem in critically ill patients with acute kidney injury receiving CHDF. Our results indicated that a meropenem dosage of 0.5 g every 8 hours or 1 g every 12 hours was suitable in this population and for susceptible bacteria.
本研究旨在对美罗培南进行群体药代动力学（PK）分析，并探讨在接受持续血液透析滤过（CHDF）治疗的急性肾损伤重症患者中美罗培南的最佳给药策略。
在美罗培南给药开始后的第1、2和5天，给药前即刻以及给药后1、2、6和8小时采集血样。进行群体PK模型分析，并使用非线性混合效应模型软件模拟浓度-时间曲线。
纳入了我们重症监护病房中接受CHDF的21例患者，获得了350个血清浓度-时间数据点。美罗培南的药代动力学最佳用二室模型描述。典型的总清除率和室间清除率值分别为4.22 L/h和7.84 L/h，而中央室和外周室的分布容积分别为14.82 L和11.75 L。估计肾小球滤过率被确定为美罗培南总清除率的显著协变量。在接受CHDF的肾衰竭患者模拟中，剂量受估计肾小球滤过率影响；每8小时0.5 g或每12小时1 g的剂量显示，对于最低抑菌浓度≤2 mg/L的细菌，达到100%时间高于最低抑菌浓度的达标概率。
为接受CHDF的急性肾损伤重症患者建立了美罗培南的群体PK模型。我们的结果表明，每8小时0.5 g或每12小时1 g的美罗培南剂量适用于该人群和易感细菌。
