Bellmann Romuald, Kuchling Gerald, Dehghanyar Pejman, Zeitlinger Markus, Minar Erich, Mayer Bernhard X, Müller Markus, Joukhadar Christian
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Austria.
Br J Clin Pharmacol. 2004 May;57(5):563-8. doi: 10.1111/j.1365-2125.2004.02059.x.
The present study addressed the ability of levofloxacin to penetrate into subcutaneous adipose tissues in patients with soft tissue infection.
Tissue concentrations of levofloxacin in inflamed and healthy subcutaneous adipose tissue were measured in six patients by microdialysis after administration of a single intravenous dose of 500 mg. Levofloxacin was assayed by high-performance liquid chromatography.
The mean concentration vs time profile of free levofloxacin in plasma was identical to that in inflamed and healthy tissues. The ratios of the mean area under the free levofloxacin concentration vs time curve from 0 to 10 h (AUC(0,10 h)) in tissue to that in plasma were 1.2 +/- 1.0 for inflamed and 1.1 +/- 0.6 for healthy subcutaneous adipose tissue (mean +/- SD). The mean difference in the ratio of the AUC(tissue) : AUC(plasma) for inflamed and healthy tissue was 0.09 (95% confidence interval -0.58, 0.759, P > 0.05). Interindividual variability in tissue penetration was high, as indicated by a coefficient of variation of approximately 82% for AUC(tissue) : AUC(plasma) ratios.
The penetration of levofloxacin into tissue appears to be unaffected by local inflammation. Our plasma and tissue data suggest that an intravenous dose of 500 mg levofloxacin provides effective antibacterial concentrations at the target site. However, in treatment resistant patients, tissue concentrations may be sub-therapeutic.
本研究探讨左氧氟沙星在软组织感染患者中渗透至皮下脂肪组织的能力。
对6例患者单次静脉注射500mg左氧氟沙星后，采用微透析法测定左氧氟沙星在炎症及健康皮下脂肪组织中的浓度。采用高效液相色谱法测定左氧氟沙星含量。
血浆中游离左氧氟沙星的平均浓度-时间曲线与炎症及健康组织中的曲线相同。炎症皮下脂肪组织中游离左氧氟沙星浓度-时间曲线从0至10小时的平均曲线下面积（AUC(0,10 h)）与血浆中该曲线下面积的比值为1.2±1.0，健康皮下脂肪组织为1.1±0.6（均值±标准差）。炎症组织与健康组织的AUC(组织) : AUC(血浆)比值的平均差异为0.09（95%置信区间-0.58，0.759，P>0.05）。AUC(组织) : AUC(血浆)比值的变异系数约为82%，表明组织渗透的个体间变异性较高。
左氧氟沙星向组织中的渗透似乎不受局部炎症影响。我们的血浆和组织数据表明，静脉注射500mg左氧氟沙星可在靶部位提供有效的抗菌浓度。然而，对于治疗抵抗的患者，组织浓度可能低于治疗水平。
