Brunner Martin, Stabeta Heino, Möller Jan-Georg, Schrolnberger Claudia, Erovic Boban, Hollenstein Ursula, Zeitlinger Markus, Eichler Hans Georg, Müller Markus
Department of Clinical Pharmacology, University of Vienna Medical School, Austria.
Antimicrob Agents Chemother. 2002 Dec;46(12):3724-30. doi: 10.1128/AAC.46.12.3724-3730.2002.
To characterize the potential of ciprofloxacin penetration into human soft tissues following intravenous (i.v.) and oral (p.o.) administration, we measured the free ciprofloxacin concentrations in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue by microdialysis. In addition, ciprofloxacin concentrations were measured in cantharis-induced skin blisters, saliva, and capillary plasma and were compared to the total concentrations in venous plasma. Furthermore, a pharmacodynamic in vitro model was used to simulate in vivo pharmacokinetics in bacterial culture. Eight healthy volunteers received ciprofloxacin in an open randomized crossover fashion either as a single i.v. infusion of 400 mg over 60 min or as a single p.o. dose of 500 mg. For both tissues the mean areas under the concentration-time curves (AUCs) for interstitial space fluid (AUC(interstitial fluid)s) were significantly lower than the corresponding AUC(plasma)s, with AUC(interstitial fluid)/AUC(plasma) ratios ranging from 0.38 to 0.68. For skeletal muscle, the AUC(interstitial fluid) was significantly higher after administration of 400 mg i.v. than after administration of 500 mg p.o., with a ratio of the AUC after p.o. administration/AUC after i.v. administration of 0.64. The ratio of the concentration in skeletal muscle/concentration in plasma increased over the entire observation period, implying that ciprofloxacin concentrations were not at steady state. The ratio of the concentration in skin blister fluid/concentration in plasma reached values above 4, indicating a preferential penetration of ciprofloxacin into inflamed lesions. The concentrations in saliva and capillary blood were similar to the corresponding total levels in plasma. In vitro both in vivo ciprofloxacin concentration-time profiles were equally effective against select bacterial strains. In conclusion, single-dose administration of two bioequivalent dosage forms of ciprofloxacin might lead to differences in target site pharmacokinetics. These differences, however, are not related to a difference in target site pharmacodynamics.
为了描述静脉注射（i.v.）和口服（p.o.）环丙沙星后其渗透进入人体软组织的潜力，我们通过微透析测量了骨骼肌和皮下脂肪组织间质液中的游离环丙沙星浓度。此外，还测量了斑蝥素诱导的皮肤水疱、唾液和毛细血管血浆中的环丙沙星浓度，并与静脉血浆中的总浓度进行比较。此外，还使用了体外药效学模型来模拟细菌培养中的体内药代动力学。8名健康志愿者以开放随机交叉方式接受环丙沙星，要么静脉注射400mg，持续60分钟，要么口服500mg单剂量。对于两种组织，间质液浓度-时间曲线下的平均面积（AUC（间质液））均显著低于相应的AUC（血浆），AUC（间质液）/AUC（血浆）比值在0.38至0.68之间。对于骨骼肌，静脉注射400mg后AUC（间质液）显著高于口服500mg后，口服给药后的AUC/静脉注射给药后的AUC比值为0.64。在整个观察期内，骨骼肌中的浓度/血浆中的浓度比值增加，这意味着环丙沙星浓度未达到稳态。皮肤水疱液中的浓度/血浆中的浓度比值达到4以上，表明环丙沙星优先渗透到炎症病变中。唾液和毛细血管血中的浓度与血浆中相应的总水平相似。在体外，两种体内环丙沙星浓度-时间曲线对选定的细菌菌株同样有效。总之，单剂量给予两种生物等效剂型的环丙沙星可能导致靶位药代动力学的差异。然而，这些差异与靶位药效学的差异无关。
