Thallinger Christiane, Buerger Cornelia, Plock Nele, Kljucar Sascha, Wuenscher Sonja, Sauermann Robert, Kloft Charlotte, Joukhadar Christian
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
J Antimicrob Chemother. 2008 Jan;61(1):173-6. doi: 10.1093/jac/dkm431. Epub 2007 Nov 13.
In the present study, we examined whether differences in the severity of sepsis translate to differences in the pharmacokinetic profile of linezolid in plasma and the interstitium of target tissues after a single intravenous dose of 600 mg by means of the microdialysis technique.
A total of 24 patients were included in the trial. Sixteen patients suffered from septic shock and eight patients presented with severe sepsis. Sepsis was diagnosed and verified according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Historic data derived from a previous study determining the pharmacokinetic profiles of linezolid in tissues and plasma in young healthy volunteers served as controls.
In the present study, the AUC for free linezolid from 0 to 24 h (fAUC(0-24)) ranged from 50 to 71 mg x h/L after single-dose administration in patients presenting with severe sepsis or septic shock. The mathematically extrapolated fAUC(0-24) ranged from 100 to 146 mg x h/L for twice-daily administration and a dosing interval of 12 h. No statistically significant difference in key pharmacokinetic parameters was detected between patients suffering from severe sepsis and septic shock (P > 0.05).
These data indicated that the severity of sepsis has no substantial effect on the pharmacokinetic profile of linezolid in plasma and in the interstitium of soft tissues.
在本研究中，我们通过微透析技术研究了在单次静脉注射600mg利奈唑胺后，脓毒症严重程度的差异是否会转化为血浆和靶组织间质中利奈唑胺药代动力学特征的差异。
共有24名患者纳入试验。16名患者患有感染性休克，8名患者患有严重脓毒症。脓毒症根据美国胸科医师学会/危重病医学会共识会议委员会的标准进行诊断和核实。来自先前一项确定年轻健康志愿者组织和血浆中利奈唑胺药代动力学特征的研究的历史数据用作对照。
在本研究中，严重脓毒症或感染性休克患者单剂量给药后，游离利奈唑胺0至24小时的药时曲线下面积（fAUC(0 - 24)）范围为50至71mg·h/L。每日两次给药且给药间隔为12小时时，数学外推的fAUC(0 - 24)范围为100至146mg·h/L。严重脓毒症患者和感染性休克患者之间未检测到关键药代动力学参数的统计学显著差异（P > 0.05）。
这些数据表明，脓毒症的严重程度对血浆和软组织间质中利奈唑胺的药代动力学特征没有实质性影响。
