Hollenstein U M, Brunner M, Schmid R, Müller M
Department of Clinical Pharmacology, Vienna University Hospital, Vienna, Austria.
Int J Obes Relat Metab Disord. 2001 Mar;25(3):354-8. doi: 10.1038/sj.ijo.0801555.
To investigate whether weight adjusted ciprofloxacin dosing results in comparable target site concentrations in obese and lean subjects.
Comparative study in two populations.
Twelve obese subjects (mean weight 122+/-22.6 kg, 28-52 y, male∶female ratio 4∶8) and 12 age- and sex-matched lean controls (mean weight 59+/-8.6 kg).
Sampling of interstitial space fluid by means of calibrated in vivo microdialysis after a weight-adjusted intravenous bolus dose of 2.85 mg/kg ciprofloxacin. Analysis of drug concentration by high pressure liquid chromatography.
We found significantly higher peak and trough levels of ciprofloxacin in plasma for obese subjects (9.97+/-5.64 and 0.44+/-0.10 microg/ml vs 2.59+/-1.06 and 0.19+/-0.09 microg/ml in lean subjects, P<0.05), while concentration-time curves of interstitial fluid of muscle and subcutaneous fat did not differ between the groups. Tissue penetration, expressed as AUC(tissue)/AUC(plasma) ratio was significantly lower in obese subjects (0.45+/-0.27 vs 0.82+/-0.36, P<0.01).
We conclude that the penetration process into the interstitial space fluid is impaired in obese subjects. Therefore antibiotic doses need not be adjusted for an increase in fat/water ratio. Weight-adjusted dosing based on actual body weight will yield adequate tissue levels for ciprofloxacin.
研究根据体重调整环丙沙星给药剂量后，肥胖和消瘦受试者的靶部位浓度是否具有可比性。
对两组人群进行的对比研究。
12名肥胖受试者（平均体重122±22.6 kg，28 - 52岁，男∶女比例为4∶8）和12名年龄及性别匹配的消瘦对照者（平均体重59±8.6 kg）。
在静脉注射2.85 mg/kg体重调整剂量的环丙沙星后，通过校准的体内微透析技术采集组织间隙液样本。采用高压液相色谱法分析药物浓度。
我们发现肥胖受试者血浆中环丙沙星的峰浓度和谷浓度显著更高（肥胖受试者分别为9.97±5.64和0.44±0.10 μg/ml，消瘦受试者分别为2.59±1.06和0.19±0.09 μg/ml，P<0.05），而两组肌肉和皮下脂肪组织间隙液的浓度 - 时间曲线并无差异。以AUC(组织)/AUC(血浆)比值表示的组织穿透率在肥胖受试者中显著更低（0.45±0.27 vs 0.82±0.36，P<0.01）。
我们得出结论，肥胖受试者进入组织间隙液的穿透过程受损。因此，无需因脂肪/水比例增加而调整抗生素剂量。基于实际体重进行体重调整给药将使环丙沙星在组织中达到足够的浓度水平。
