Population pharmacokinetics of cefepime in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)
Population pharmacokinetics of cefepime in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)
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DOI：
10.1016/j.ijantimicag.2021.106466
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发表时间：
2021-11-24
影响因子：
10.8
通讯作者：
Fraser, John F.
中科院分区：
文献类型：
--
作者：
Cheng, Vesa;Abdul-Aziz, Mohd H.;Fraser, John F.
目的：本研究旨在描述体外膜肺氧合（ECMO）过程中头孢吡肟的群体药代动力学（PK），并通过给药模拟，确定最大有效和安全的给药策略。方法：在ECMO患者中测量系列头孢吡肟血药浓度，并使用群体PK方法与Pmetrics（R）分析数据。使用给药模拟确定达到8-20 mg/L目标谷浓度（C-min）的最佳给药策略。6例患者入组，其中1例接受肾脏替代治疗。头孢吡肟最好用二室模型描述，总体重和肌酐清除率（CrCL）是PK参数的重要预测因素。平均清除率和中心分布容积分别为2.42 L/h和15.09 L。结果：根据模拟，CrCL为120 mL/min的患者接受1 g 8小时给药，达到40-44%的疗效概率（C-min > 8 mg/L）和1-6%的毒性概率（C-min > 20 mg/L）。CrCL <30 mL/min和<65 mL/min的患者接受1 g 12小时给药后，疗效概率分别为84-92%和46-53%，毒性概率分别为8-44%和1-8%。模拟表明，降低患者weight.Conclusion：本研究报告减少头孢吡肟清除率的患者接受ECMO，导致头孢吡肟毒性的风险增加的概率较低的疗效和较高的概率的毒性。为避免药物蓄积，ECMO危重患者应采用改良给药方案。临床医生在治疗敏感性较低的微生物和ECMO肾清除率降低的患者时，应采用治疗药物监测。(C)2021爱思唯尔有限公司和国际抗菌药物化学治疗学会。All rights reserved.
Objectives: This study aimed to describe the population pharmacokinetics (PK) of cefepime during extracorporeal membrane oxygenation (ECMO) and through dosing simulations, identify a maximally effective and safe dosing strategy.Methods: Serial cefepime plasma concentrations were measured in patients on ECMO, and data were analysed using a population PK approach with Pmetrics (R). Dosing simulations were used to identify the optimal dosing strategy that achieved target trough concentrations (C-min) of 8-20 mg/L. Six patients were enrolled, of which one was receiving renal replacement therapy. Cefepime was best described in a two-compartment model, with total body weight and creatinine clearance (CrCL) as significant predictors of PK parameters. The mean clearance and central volume of distribution were 2.42 L/h and 15.09 L, respectively.Results: Based on simulations, patients with CrCL of 120 mL/min receiving 1 g 8-hourly dosing achieved a 40-44% probability of efficacy (C-min > 8 mg/L) and 1-6% toxicity (C-min > 20 mg/L). Patients with CrCL 30 mL/min and 65 mL/min receiving 1 g 12-hourly dosing achieved an 84-92% and 46-53% probability of efficacy and 8-44% and 1-8% probability of toxicity, respectively. Simulations demonstrated a lower probability of efficacy and higher probability of toxicity with decreasing patient weight.Conclusion: This study reported reduced cefepime clearance in patients receiving ECMO, resulting in an increased risk of cefepime toxicity. To avoid drug accumulation, modified dosing regimens should be used in critically ill patients on ECMO. Clinicians should adopt therapeutic drug monitoring when treating less susceptible organisms and in patients with reduced renal clearance on ECMO. (C) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.