Davey P G, Precious E, Winter J
Department of Clinical Pharmacology, Ninewells Hospital, Dundee, UK.
J Antimicrob Chemother. 1991 Mar;27(3):335-41. doi: 10.1093/jac/27.3.335.
Simultaneous bronchial biopsy and serum samples were obtained from 14 patients after a single oral dose of 200 mg ofloxacin and from ten patients during the course of multiple dose oral treatment, (200 mg ofloxacin bd) for acute exacerbations of chronic bronchitis. Duplicate bronchial samples from different parts of the lung were obtained from five patients. Concentrations in bronchial mucosa were equal to or higher than serum concentrations. There were no statistically significant differences in concentrations after single or multiple doses but there appeared to be a trend towards higher concentrations after multiple doses. After a single dose bronchial and serum concentrations ranged from 1.3 to 15.5 mg/kg and from 0.1 to 5.0 mg/l, respectively, between 1 and 6 h after dosing. After multiple dosing of patients with acute exacerbations of chronic bronchitis bronchial and serum concentrations ranged from 1.7 to 21.0 mg/kg and 1.0 to 6.1 mg/l, respectively between 1 and 12 h. The percentage difference in ofloxacin concentrations in five duplicate bronchial samples from different parts of the lung was -4%, (95% confidence intervals +22% to -30%). Thus, the model of bronchial sampling after single dosing of patients before diagnostic bronchoscopy gave results that were similar to those obtained after multiple dosing of patients with acute exacerbations of chronic bronchitis. After multiple dosing ofloxacin concentrations were greater than 1 mg/l or greater than 1 mg/kg in serum and bronchial mucosa throughout the dosing interval, which is above the MIC for most respiratory pathogens.
在14例单次口服200mg氧氟沙星的患者以及10例接受多剂量口服治疗（200mg氧氟沙星，每日两次）以治疗慢性支气管炎急性加重的患者中，同时获取了支气管活检样本和血清样本。从5例患者中获取了来自肺不同部位的两份支气管样本。支气管黏膜中的浓度等于或高于血清浓度。单次或多次给药后的浓度在统计学上无显著差异，但多次给药后似乎有浓度升高的趋势。单次给药后，给药后1至6小时内，支气管和血清浓度分别为1.3至15.5mg/kg和0.1至5.0mg/L。在慢性支气管炎急性加重患者多次给药后，1至12小时内支气管和血清浓度分别为1.7至21.0mg/kg和1.0至6.1mg/L。来自肺不同部位的5份重复支气管样本中氧氟沙星浓度的百分比差异为-4%（95%置信区间为+22%至-30%）。因此，在诊断性支气管镜检查前对患者单次给药后进行支气管采样的模型所得到的结果与慢性支气管炎急性加重患者多次给药后得到的结果相似。多次给药后，在整个给药间隔内，血清和支气管黏膜中的氧氟沙星浓度均大于1mg/L或大于1mg/kg，这高于大多数呼吸道病原体的最低抑菌浓度。
