Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand.
School of Pharmaceutical Sciences, University of Phayao, Muang, Thailand.
Pharmacotherapy. 2021 Jul;41(7):572-597. doi: 10.1002/phar.2597. Epub 2021 Jun 18.
The objectives of this study were (i) to determine the population pharmacokinetic (PK) of imipenem in critically ill patients with life-threatening severe infections, (ii) to investigate the impact of extracorporeal membrane oxygenation (ECMO) on the population PK of imipenem during support with ECMO compared to those without ECMO support, and (iii) to assess the probability of target attainment (PTA) for finding the optimal dosage regimens of imipenem in critically ill patients with life-threatening severe infections.
Open-label, PK study.
Academic tertiary care medical center.
Fifty critically ill patients with or without ECMO by pooling data from previously published studiesand unpublished data from 14 patients.
The population PK of imipenem was determined using NONMEM and a Monte Carlo simulation was performed to determine the PTAs of achieving 40% and 75% exposure times during which the plasma drug concentrations remained above the MIC.
The values of volume of distribution and total clearance were 30.5 L and 13.3 L/h, respectively. The ECMO circuit did not show a significant influence on the PK parameters of imipenem. For pathogens with a MIC of 4 mg/L, the PTA target of 75% fT>MIC in patients with normal renal function was achieved when the imipenem was administered by a 4-h infusion of 1 g q6h.
The ECMO circuit had little effect on enhancing the PK changes of imipenem that had already occurred in these patients. A high dosage of imipenem may be required for achieving the PK/pharmacodynamic targets against less susceptible pathogens, however, the dosage regimens in patients with renal impairment may not need to be as high as those required in patients with normal renal function. ClinicalTrials.gov: NCT03858387.
本研究的目的是：（i）确定生命垂危的严重感染危重症患者中亚胺培南的群体药代动力学（PK）；（ii）与无 ECMO 支持的患者相比，调查体外膜氧合（ECMO）对 ECMO 支持下亚胺培南群体 PK 的影响；（iii）评估达到目标的概率（PTA），以找到生命垂危的严重感染危重症患者中最佳亚胺培南剂量方案。
开放标签 PK 研究。
学术三级护理医疗中心。
通过合并先前发表的研究数据和来自 14 名患者的未发表数据，共纳入 50 名患有或不患有 ECMO 的危重症患者。
使用 NONMEM 确定亚胺培南的群体 PK，并进行蒙特卡罗模拟以确定达到 40%和 75%暴露时间的 PTA，在此期间，血浆药物浓度保持在 MIC 以上。
分布容积和总清除率分别为 30.5 L 和 13.3 L/h。ECMO 回路对亚胺培南 PK 参数没有显著影响。对于 MIC 为 4 mg/L 的病原体，在肾功能正常的患者中，当亚胺培南以 1 g q6h 的 4 小时输注给予时，75%fT>MIC 的 PTA 目标可达到。
ECMO 回路对已经发生在这些患者中的亚胺培南 PK 变化的影响不大。对于敏感性较低的病原体，可能需要较高剂量的亚胺培南才能达到 PK/药效学目标，但肾功能不全患者的剂量方案可能不需要像肾功能正常患者那样高。ClinicalTrials.gov：NCT03858387。
