Service des réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France Equipe d'Accueil 2992, Faculté de Médecine de Nîmes, Université de Montpellier, Nimes, France Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia
Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
J Antimicrob Chemother. 2016 Jun;71(6):1643-50. doi: 10.1093/jac/dkw043. Epub 2016 Mar 7.
Whilst commonly performed in ICUs, renal replacement therapies (RRTs) differ in their solute clearances. There is a paucity of data on ciprofloxacin clearances in different RRT techniques. The aim of this study was to compare the population pharmacokinetics of ciprofloxacin during equal doses of continuous venovenous haemofiltration (CVVHF) and continuous venovenous haemodiafiltration (CVVHDF) in septic patients.
Patients receiving 400 mg of ciprofloxacin intravenously 8 or 12 hourly and undergoing either CVVHF or CVVHDF were eligible. Up to 10 blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo simulation was undertaken using Pmetrics.
Eighteen sampling intervals were included (8 CVVHDF and 10 CVVHF) from 11 patients (6 patients having sampling during both RRT modes). A two-compartment linear model best described the data. Increasing patient weight was the only covariate associated with increasing drug clearance. The mean (SD) parameter estimates were: clearance, 10.7 (5.3) L/h; volume of distribution of the central compartment, 21.3 (11.3) L; rate constant for drug distribution from the central compartment to the peripheral compartment, 10.9 (4.3) L/h; and rate constant for drug distribution from the peripheral compartment to the central compartment, 2.3 (1.8) L/h. After accounting for patient weight, the mean ciprofloxacin clearance was not statistically different between CVVHF and CVVHDF [11.8 (9.9) and 10.3 (7.4) L/h, respectively, P = 0.43].
The present study indicates a high pharmacokinetic variability of ciprofloxacin during CVVHF and CVVHDF with no significant differences in clearance apparent. Based on patient weight, higher ciprofloxacin dosing regimens should be used in critically ill patients when difficult-to-treat pathogens are suspected.
尽管肾脏替代疗法（RRT）在 ICU 中经常使用，但它们的溶质清除率却有所不同。关于不同 RRT 技术中环丙沙星清除率的数据很少。本研究的目的是比较脓毒症患者接受连续静脉-静脉血液滤过（CVVHF）和连续静脉-静脉血液透析滤过（CVVHDF）时相同剂量下环丙沙星的群体药代动力学。
符合条件的患者接受静脉注射 400mg 环丙沙星，每 8 或 12 小时一次，并接受 CVVHF 或 CVVHDF 治疗。在一个给药间隔内采集了多达 10 个血样，并通过验证的色谱法进行了分析。使用 Pmetrics 进行群体药代动力学分析和蒙特卡罗模拟。
纳入了 11 名患者的 18 个采样间隔（8 个 CVVHDF 和 10 个 CVVHF）（6 名患者在两种 RRT 模式下均有采样）。二室线性模型最能描述数据。患者体重增加是唯一与药物清除率增加相关的协变量。平均（SD）参数估计值为：清除率 10.7（5.3）L/h；中央隔室分布容积 21.3（11.3）L；药物从中央隔室向周围隔室分布的速率常数 10.9（4.3）L/h；药物从周围隔室向中央隔室分布的速率常数 2.3（1.8）L/h。在考虑患者体重后，CVVHF 和 CVVHDF 之间环丙沙星清除率无统计学差异[分别为 11.8（9.9）和 10.3（7.4）L/h，P=0.43]。
本研究表明，在 CVVHF 和 CVVHDF 期间，环丙沙星的药代动力学变异性很大，但清除率没有明显差异。基于患者体重，如果怀疑有难以治疗的病原体，应在重症患者中使用更高的环丙沙星剂量方案。
