Marín P, Fernández-Varón E, Escudero E, Vancraeynest D, Cárceles C M
Department of Pharmacology, Faculty of Veterinary Medicine, University of Murcia, Murcia, Spain.
J Vet Pharmacol Ther. 2008 Feb;31(1):77-82. doi: 10.1111/j.1365-2885.2007.00927.x.
The single-dose disposition kinetics of orbifloxacin were determined in clinically normal rabbits (n=6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg bodyweight. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of orbifloxacin against 30 strains of Staphylococcus aureus from several European countries was performed in order to compute pharmacodynamic surrogate markers. The concentration-time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution (V(ss)) and total body clearance (Cl) of orbifloxacin after i.v. administration were estimated to be 1.71+/-0.38 L/kg and 0.91+/-0.20 L/h x kg, respectively. Following s.c. and i.m. administration orbifloxacin achieved maximum plasma concentrations of 2.95+/-0.82 and 3.24+/-1.33 mg/L at 0.67+/-0.20 and 0.65+/-0.12 h, respectively. The absolute bio-availabilities after s.c. and i.m. routes were 110.67+/-11.02% and 109.87+/-8.36%, respectively. Orbifloxacin showed a favourable pharmacokinetic profile in rabbits. However, on account of the low AUC/MIC and C(max)/MIC indices obtained, its use by i.m. and s.c. routes against the S. aureus strains assayed in this study cannot be recommended given the risk of selection of resistant populations.
在临床正常的兔子（n = 6）中，静脉注射（i.v.）、皮下注射（s.c.）和肌肉注射（i.m.）5mg/kg体重的奥比沙星后，测定了其单剂量处置动力学。通过高效液相色谱荧光检测法测定奥比沙星浓度。为了计算药效学替代指标，对来自几个欧洲国家的30株金黄色葡萄球菌进行了奥比沙星的最低抑菌浓度（MIC）测定。通过房室和非房室动力学方法分析浓度-时间数据。静脉注射后，奥比沙星的稳态分布容积（V(ss)）和全身清除率（Cl）估计分别为1.71±0.38L/kg和0.91±0.20L/h·kg。皮下注射和肌肉注射后，奥比沙星分别在0.67±0.20小时和0.65±0.12小时达到最大血浆浓度2.95±0.82mg/L和3.24±1.33mg/L。皮下注射和肌肉注射途径后的绝对生物利用度分别为110.67±11.02%和109.87±8.36%。奥比沙星在兔子中显示出良好的药代动力学特征。然而，由于获得的AUC/MIC和C(max)/MIC指数较低，考虑到有选择耐药菌群体的风险，不建议在本研究中通过肌肉注射和皮下注射途径使用其对抗所检测的金黄色葡萄球菌菌株。
