Population Pharmacokinetic Analysis of Meropenem in Critically Ill Patients With Acute Kidney Injury Treated With Continuous Hemodiafiltration
Population Pharmacokinetic Analysis of Meropenem in Critically Ill Patients With Acute Kidney Injury Treated With Continuous Hemodiafiltration
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DOI：
10.1097/ftd.0000000000000741
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发表时间：
2020-08-01
影响因子：
2.5
通讯作者：
Ishii, Itsuko
中科院分区：
文献类型：
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作者：
Niibe, Yoko;Suzuki, Tatsuya;Ishii, Itsuko
背景：本研究的目的是对美罗培南进行群体药代动力学(PK)分析，探讨美罗培南在接受连续性血液透析滤过(CHDF)治疗的急性肾损伤危重患者中的最佳给药策略。方法：分别于美罗培南开始给药后第1、2、5天、给药前、给药后1、2、6、8小时采集血样。用非线性混合效应模型软件进行群体PK模型分析和浓度-时间曲线模拟。结果：纳入21例在重症监护病房接受CHDF治疗的患者，获得350个血药浓度-时间数据点。美罗培南的pKs符合二室模型。典型的总间隙和室间间隙分别为4.2 2 L/h和7.84 L/h，中心室容积和周边室容积分布分别为14.82 L和11.75 L。估计的肾小球滤过率被确定为美罗培南总清除量的重要协变量。在肾功能衰竭患者接受CHDF治疗的模拟中，剂量受到估计的肾小球滤过率的影响；每8小时0.5g或每12小时1g的剂量表明，达到目标的可能性达到100%，超过具有最低抑制浓度的细菌的最低抑制浓度
Background: 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). Methods: 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. Results: 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