Population Pharmacokinetics of Vancomycin under Continuous Renal Replacement Therapy using a Polymethylmethacrylate Hemofilter
Population Pharmacokinetics of Vancomycin under Continuous Renal Replacement Therapy using a Polymethylmethacrylate Hemofilter
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使用聚甲基丙烯酸甲酯滤血器连续肾脏替代治疗下万古霉素的群体药代动力学
DOI：
10.1097/ftd.0000000000000721
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发表时间：
2019
影响因子：
2.5
通讯作者：
Ishii Itsuko
中科院分区：
文献类型：
--
作者：
Yamazaki Shingo;Tatebe Mizuki;Fujiyoshi Masachika;Hattori Noriyuki;Suzuki Tatsuya;Takatsuka Hirokazu;Uchida Masashi;Suzuki Takaaki;Ishii Itsuko
背景：尽管重症患者在脓毒症治疗期间经常进行连续性血液透析滤过（CHDF），但使用聚甲基丙烯酸甲酯血液滤过器（PMMA-CHDF）进行CHDF期间万古霉素（VCM）的药代动力学尚未揭示。在这项研究中，作者旨在描述VCM在接受PMMA-CHDF的危重患者中的群体药代动力学，并阐明其血液滤过器清除率（CL血液滤过器）。方法：这项单中心、回顾性研究招募了2008年至2016年期间在千叶大学医院重症监护室接受PMMA-CHDF期间静脉内VCM治疗的患者。进行人群分析，并评估CL血液滤过器。中位体重（BW）和序贯器官衰竭评估（SOFA）评分分别为63 kg和15。CHDF的平均条件为血液流速为107.5±18.3 mL/min，流出液流速为26.3±6.3 mL/kg/h。平均参数估计值为中央室分布容积（V 1），59.1 L;中央室清除率（CL 1），1.35 L/h;外周室分布容积（V 2），56.1 L;外周室清除率（CL 2），3.65 L/h。BW和SOFA评分分别与V1（P< 0.05）和CL 1（P< 0.05）显著相关，因此被选为最终模型的协变量。达到浓度-时间曲线下目标面积/最小抑制浓度≥ 400的VCM估计剂量为27.1 mg/kg（负荷）和9.7 mg/kg（每24小时一次）（维持）;这些剂量受BW和SOFA评分的影响。8例患者的平均CL血液滤过器为1.35 L/h，与CL 1相似。结论：作者阐明了PMMA-CHDF患者VCM的药代动力学和CL血液滤过器。在接受CHDF的患者中，VCM的PK似乎不仅随CHDF设置和BW而变化，而且随SOFA评分而变化。
Background:Although continuous hemodiafiltration (CHDF) is often performed in critically ill patients during sepsis treatment, the pharmacokinetics of vancomycin (VCM) during CHDF with a polymethylmethacrylate hemofilter (PMMA-CHDF) have not been revealed. In this study, the authors aimed to describe the population pharmacokinetics of VCM in critically ill patients undergoing PMMA-CHDF and clarify its hemofilter clearance (CL hemofilter).Methods:This single-center, retrospective study enrolled patients who underwent intravenous VCM therapy during PMMA-CHDF at the intensive care unit of Chiba University Hospital between 2008 and 2016. A population analysis was performed, and CL hemofilter was assessed.Results:Twenty-five patients were enrolled. Median body weight (BW) and Sequential Organ Failure Assessment (SOFA) score were 63 kg and 15, respectively. Mean conditions for CHDF were 107.5±18.3 mL/min for blood flow rate and 26.3±6.3 mL/kg/h for effluent flow rate. The mean parameter estimates were distribution volume of the central compartment (V 1), 59.1 L; clearance of the central compartment (CL 1), 1.35 L/h; distribution volume of the peripheral compartment (V 2), 56.1 L; and clearance of the peripheral compartment (CL 2), 3.65 L/h. BW and SOFA score were significantly associated with V 1 (P< 0.05) and CL 1 (P< 0.05), respectively, and were thus selected as covariates in the final model. The estimated dosage of VCM to achieve a target area under the concentration–time curve/minimum inhibitory concentration≥ 400 was 27.1 mg/kg for loading and 9.7 mg/kg every 24 hours for maintenance; these dosages were affected by BW and SOFA score. Mean CL hemofilter obtained from 8 patients was 1.35 L/h, which was similar to CL 1.Conclusions:The authors clarified the pharmacokinetics and CL hemofilter of VCM in PMMA-CHDF patients. The PK of VCM in patients undergoing CHDF appeared to vary not only with the CHDF setting and BW but also with SOFA score.