Ciprofloxacin use in critically ill patients: pharmacokinetic and pharmacodynamic approaches
Ciprofloxacin use in critically ill patients: pharmacokinetic and pharmacodynamic approaches
复制标题
DOI：
10.1016/j.ijantimicag.2008.05.019
复制
发表时间：
2008-12-01
影响因子：
10.8
通讯作者：
Saivin, Sylvie
中科院分区：
文献类型：
--
作者：
Conil, Jean-Marie;Georges, Bernard;Saivin, Sylvie
本研究的目的是利用人群方法评估环丙沙星在重症监护患者中的作用。70例患者接受环丙沙星治疗。第1天，在12小时内采集3至8份血液样本。比较药物峰值浓度（C-max）和24 h浓度-时间曲线下面积（AUC）与测定药物敏感性的法国断点（French breakpoint）。然后进行了群体药代动力学建模方法。带比例误差模型的双室开放模型最能拟合数据。消除常数率与科克罗夫特肌酐清除率之间存在一定的关系。环丙沙星清除率为13.6 +/- 5.8 L/h，分布容积为62.0 +/- 10.7 L，环丙沙星半衰期为3.7 +/- 1.8 h。最小抑制浓度（MIC）为1 mg/L时，抑制比（IR）为>= 8的病例仅占10.8%，AUC/MIC比（AUIC）为42.0 +/- 36。总之，本研究强调Cockcroft清除率显著影响环丙沙星的消除。环丙沙星靶血药浓度、IR和AUIC在标准给药方案下很少达到。在危重患者中，观察到的药代动力学变异性是导致环丙沙星浓度过低的主要原因，强调了治疗监测的必要性。(C) 2008 Elsevier b.v.与International Society of Chemotherapy。版权所有。
The objective of this study was to evaluate the properties of ciprofloxacin in intensive care patients using a population approach. Seventy patients received ciprofloxacin. On Day 1, three to eight blood samples were taken over a 12-h period. Peak drug concentration (C-max) and 24-h area under the concentration-time curve (AUC) were compared with the French breakpoint de. ning antibiotic susceptibility. A population pharmacokinetic modelling approach was then carried out. A two-compartment open model with a proportional error model best fitted the data. A relationship between the elimination constant rate and the Cockcroft creatinine clearance was found. Ciprofloxacin clearance was 13.6 +/- 5.8 L/h, the volume of distribution was 62.0 +/- 10.7 L and the ciprofloxacin half-life was 3.7 +/- 1.8 h. When the minimum inhibitory concentration (MIC) was equal to 1 mg/L the inhibitory ratio (IR) was >= 8 in only 10.8% of cases, and the AUC/MIC ratio (AUIC) was 42.0 +/- 36. In conclusion, this study highlights that the Cockcroft clearance significantly influences ciprofloxacin elimination. Target plasma concentrations for ciprofloxacin, the IR and AUIC were rarely reached with a standard dosing regimen. In critically ill patients, the observed pharmacokinetic variability is mainly responsible for the overly frequent low concentrations of ciprofloxacin, emphasising the need for therapeutic monitoring. (C) 2008 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.