Rodvold Keith A, Danziger Larry H, Gotfried Mark H
College of Pharmacy, University of Illinois, Chicago, Illinois, USA.
Antimicrob Agents Chemother. 2003 Aug;47(8):2450-7. doi: 10.1128/AAC.47.8.2450-2457.2003.
The purpose of this study was to compare the concentrations of levofloxacin and azithromycin in steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) after intravenous administration. Thirty-six healthy, nonsmoking adult subjects were randomized to either intravenous levofloxacin (500 or 750 mg) or azithromycin (500 mg) once daily for five doses. Venipuncture and bronchoscopy with bronchoalveolar lavage were performed in each subject at either 4, 12, or 24 h after the start of the last antibiotic infusion. The mean concentrations of levofloxacin and azithromycin in plasma were similar to those previously published. The dosing regimens of levofloxacin achieved significantly (P < 0.05) higher concentrations in steady-state plasma than azithromycin during the 24 h after drug administration. The respective mean (+/- standard deviation) concentrations at 4, 12, and 24 h in ELF for 500 mg of levofloxacin were 11.01 +/- 4.52, 2.50 +/- 0.97, and 1.24 +/- 0.55 micro g/ml; those for 750 mg of levofloxacin were 12.94 +/- 1.21, 6.04 +/- 0.39, and 1.73 +/- 0.78 micro g/ml; and those for azithromycin were 1.70 +/- 0.74, 1.27 +/- 0.47, and 2.86 +/- 1.75 micro g/ml. The differences in concentrations in ELF among the two levofloxacin groups and azithromycin were significantly (P < 0.05) higher at the 4- and 12-h sampling times. The respective concentrations in AM for 500 mg of levofloxacin were 83.9 +/- 53.2, 18.3 +/- 6.7, and 5.6 +/- 3.2 micro g/ml; those for 750 mg of levofloxacin were 81.7 +/- 37.0, 78.2 +/- 55.4, and 13.3 +/- 6.5 micro g/ml; and those for azithromycin were 650 +/- 259, 669 +/- 311, and 734 +/- 770 micro g/ml. Azithromycin achieved significantly (P < 0.05) higher concentrations in AM than levofloxacin at all sampling times. The concentrations in ELF and AM following intravenous administration of levofloxacin and azithromycin were higher than concentrations in plasma. Further studies are needed to determine the clinical significance of such high intrapulmonary concentrations in patients with respiratory tract infections.
本研究的目的是比较静脉给药后左氧氟沙星和阿奇霉素在稳态血浆、上皮衬液（ELF）及肺泡巨噬细胞（AM）中的浓度。36名健康、不吸烟的成年受试者被随机分为两组，分别每日静脉注射一次左氧氟沙星（500或750mg）或阿奇霉素（500mg），共注射五剂。在最后一次抗生素输注开始后的4、12或24小时，对每位受试者进行静脉穿刺及支气管肺泡灌洗的支气管镜检查。左氧氟沙星和阿奇霉素在血浆中的平均浓度与先前发表的结果相似。在给药后的24小时内，左氧氟沙星给药方案在稳态血浆中达到的浓度显著高于阿奇霉素（P<0.05）。500mg左氧氟沙星在ELF中4、12和24小时的各自平均（±标准差）浓度分别为11.01±4.52、2.50±0.97和1.24±0.55μg/ml；750mg左氧氟沙星的分别为12.94±1.21、6.04±0.39和1.73±0.78μg/ml；阿奇霉素的分别为1.70±0.74、1.27±0.47和2.86±1.75μg/ml。在4小时和12小时采样时，两个左氧氟沙星组与阿奇霉素组在ELF中的浓度差异显著（P<0.05）。500mg左氧氟沙星在AM中的各自浓度分别为83.9±53.2、18.3±6.7和5.6±3.2μg/ml；750mg左氧氟沙星为81.7±37.0、78.2±55.4和13.3±6.5μg/ml；阿奇霉素为650±259、669±311和734±770μg/ml。在所有采样时间，阿奇霉素在AM中达到的浓度显著高于左氧氟沙星（P<0.05）。静脉注射左氧氟沙星和阿奇霉素后，ELF和AM中的浓度高于血浆中的浓度。需要进一步研究以确定呼吸道感染患者肺内如此高浓度的临床意义。
