Barriere S L, Kaatz G W, Schaberg D R, Fekety R
Department of Pharmaceutical Services, University of California, Los Angeles 90024.
Antimicrob Agents Chemother. 1987 Jul;31(7):1075-8. doi: 10.1128/AAC.31.7.1075.
The pharmacokinetic disposition of vancomycin and ciprofloxacin was assessed in rabbits before the efficacy of these compounds in experimental staphylococcal endocarditis was compared. Ciprofloxacin was given in single intravenous bolus doses of 25 and 35 mg/kg and also in a multiple-dose regimen of 35 mg/kg every 6 h. Vancomycin was given in a similar manner in single doses of 17.5 and 25 mg/kg and in a multiple-dose regimen of 17.5 mg/kg every 6 h. Serum was sampled frequently after injections and analyzed by microbiologic assay for drug concentration. The pharmacokinetic parameters of clearance and steady-state volume of distribution were calculated by compartment-independent methods. These studies revealed that clearance of ciprofloxacin was reduced significantly after multiple doses (7.42 +/- 0.85 [standard deviation] versus 6.09 +/- 0.71 liters/h, P less than 0.01). Although the half-life and volume of distribution increased after multiple dosing, the differences were not statistically significant. The disposition of vancomycin following single doses was significantly altered after the 25-mg/kg dose compared with the 17.5-mg/kg dose. Half-life, clearance, and volume of distribution changed from 1.27 +/- 0.2 to 1.60 +/- 0.21 h (P less than 0.05), 0.54 +/- 0.05 to 0.39 +/- 0.04 liters/h (P less than 0.01), and 0.37 +/- 0.04 to 0.31 +/- 0.03 liters/kg (P less than 0.05), respectively. The disposition of ciprofloxacin was not altered with increases in dose size, and the disposition of vancomycin was not altered after multiple doses. If such alterations in the pharmacokinetic disposition of antimicrobial agents are unanticipated, the higher and more prolonged than expected serum concentrations may have an effect on the outcome of experimental infections.
在比较万古霉素和环丙沙星对实验性葡萄球菌性心内膜炎的疗效之前，先评估了它们在兔体内的药代动力学情况。环丙沙星以25毫克/千克和35毫克/千克的单次静脉推注剂量给药，也采用每6小时35毫克/千克的多剂量给药方案。万古霉素以类似方式给药，单次剂量为17.5毫克/千克和25毫克/千克，多剂量给药方案为每6小时17.5毫克/千克。注射后频繁采集血清，并通过微生物测定法分析药物浓度。通过非房室模型方法计算清除率和稳态分布容积等药代动力学参数。这些研究表明，多次给药后环丙沙星的清除率显著降低（7.42±0.85[标准差]对6.09±0.71升/小时，P<0.01）。虽然多次给药后半衰期和分布容积增加，但差异无统计学意义。与17.5毫克/千克剂量相比，25毫克/千克剂量的万古霉素单次给药后的处置情况有显著改变。半衰期、清除率和分布容积分别从1.27±0.2变为1.60±0.21小时（P<0.05）、0.54±0.05变为0.39±0.04升/小时（P<0.01）和0.37±0.04变为0.31±0.03升/千克（P<0.05）。环丙沙星的处置情况不会因剂量增加而改变，万古霉素多次给药后其处置情况也未改变。如果抗菌药物药代动力学处置的这种改变未被预料到，高于预期且持续时间更长的血清浓度可能会对实验性感染的结果产生影响。
