Wang Yixue, Chen Weiming, Huang Yidie, Wang Guangfei, Li Zhiping, Yan Gangfeng, Chen Chao, Lu Guoping
Department of Pediatric Critical Care Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Front Pharmacol. 2021 Aug 24;12:699191. doi: 10.3389/fphar.2021.699191. eCollection 2021.
To develop a population pharmacokinetic model of meropenem in children with sepsis receiving extracorporeal life support (ECLS) and optimize the dosage regimen based on investigating the probability of target attainment (PTA). The children with sepsis were prospectively enrolled in a pediatric intensive care unit from January 2018 to December 2019. The concentration-time data were fitted using nonlinear mixed effect model approach by NONMEM program. The stochastic simulation considering various scenarios based on proposed population pharmacokinetics model were conducted, and the PTAs were calculated to optimize the dosage regimens. A total of 25 children with sepsis were enrolled, of whom13 received ECMO, 9 received CRRT, and 4 received ECMO combined with CRRT. 12 children received a two-step 3-h infusion and 13 children received 1-h infusion. Bodyweight and creatinine clearance had significant impacts on the PK parameters. ECMO intervention was not related to the PK properties. If 100%T > MIC was chosen as target, children receiving 40 mg/kg q8h over a 3 h-infusion only reached the PTA up to 77.4%. If bacteria with MIC 2 mg/L were to be treated with meropenem and the PTA target was 50%T > MIC, a dose of 40 mg/kg q8h for 1 h infusion would be necessary. The PK properties of meropenem in septic children receiving extracorporeal life support were best described. We recommended the opitimized dosing regimens for septic children receiving ECLS depending on the PTA of PK target 50%T > MIC and 100%T > MIC, for children with sepsis during ECLS with different body weight, estimated creatinine clearance (eCRCL) and MIC of bacteria.
建立接受体外生命支持（ECLS）的脓毒症儿童美罗培南的群体药代动力学模型，并在研究目标达成概率（PTA）的基础上优化给药方案。2018年1月至2019年12月，脓毒症儿童前瞻性纳入一家儿科重症监护病房。浓度-时间数据采用NONMEM程序的非线性混合效应模型方法进行拟合。基于所提出的群体药代动力学模型，进行了考虑各种情况的随机模拟，并计算PTA以优化给药方案。共纳入25例脓毒症儿童，其中13例接受体外膜肺氧合（ECMO），9例接受连续性肾脏替代治疗（CRRT），4例接受ECMO联合CRRT。12例儿童接受3小时两步输注，13例儿童接受1小时输注。体重和肌酐清除率对药代动力学参数有显著影响。ECMO干预与药代动力学特性无关。如果选择100%T＞MIC作为目标，接受3小时输注、40mg/kg q8h的儿童仅达到77.4%的PTA。如果用美罗培南治疗MIC为2mg/L的细菌且PTA目标为50%T＞MIC，则需要1小时输注、40mg/kg q8h的剂量。最佳描述了接受体外生命支持的脓毒症儿童中美罗培南的药代动力学特性。我们根据PK目标50%T＞MIC和100%T＞MIC的PTA，为接受ECLS的脓毒症儿童推荐了优化的给药方案，适用于不同体重、估计肌酐清除率（eCRCL）和细菌MIC的ECLS期间的脓毒症儿童。
Zotero 插件
