Gotfried M H, Danziger L H, Rodvold K A
Pulmonary Associates PA, University of Arizona, Phoenix, AZ, USA.
Chest. 2001 Apr;119(4):1114-22. doi: 10.1378/chest.119.4.1114.
To determine the steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levofloxacin and ciprofloxacin.
Multiple-dose, open-label, randomized pharmacokinetic study.
Thirty-six healthy, nonsmoking adult subjects were randomized either to oral levofloxacin, 500 or 750 mg once daily for five doses, or ciprofloxacin, 500 mg q12h for nine doses.
Venipuncture, bronchoscopy, and BAL were performed in each subject at 4 h, 12 h, or 24 h after the last administered dose of antibiotic.
Mean plasma concentrations of levofloxacin and ciprofloxacin were similar to those previously reported. For once-daily dosing of levofloxacin, 500 mg, the mean (+/- SD) steady-state concentrations at 4 h, 12 h, and 24 h in ELF were 9.9 +/- 2.7 microg/mL, 6.5 +/- 2.5 microg/mL, and 0.7 +/- 0.4 microg/mL, respectively; AM concentrations were 97.9 +/- 80.0 microg/mL, 36.7 +/- 23.4 microg/mL, and 13.8 +/- 16.0 microg/mL, respectively. For levofloxacin, 750 mg, the mean steady-state concentrations in ELF were 22.1 +/- 14.9 microg/mL, 9.2 +/- 5.3 microg/mL, and 1.5 +/- 0.8 microg/mL, respectively; AM concentrations were 105.1 +/- 65.5 microg/mL, 36.2 +/- 26.1 microg/mL, and 15.1 +/- 2.0 microg/mL, respectively. The concentrations of ciprofloxacin at 4 h and 12 h in ELF were 1.9 +/- 0.9 microg/mL and 0.4 +/- 0.1 microg/mL, respectively; AM concentrations were 34.9 +/- 23.2 microg/mL and 6.8 +/- 5.9 microg/mL, respectively. The differences in the ELF concentrations of the two levofloxacin groups vs those of the ciprofloxacin group were significant (p < 0.05) at each sampling time.
Levofloxacin was more extensively distributed into intrapulmonary compartments than ciprofloxacin and achieved significantly higher steady-state concentrations in plasma and ELF during the 24 h after drug administration.
测定左氧氟沙星和环丙沙星的稳态血浆浓度、上皮衬液（ELF）浓度及肺泡巨噬细胞（AM）浓度。
多剂量、开放标签、随机药代动力学研究。
36名健康、不吸烟的成年受试者被随机分为两组，一组口服左氧氟沙星，500或750mg每日一次，共五剂；另一组口服环丙沙星，500mg每12小时一次，共九剂。
在每位受试者最后一剂抗生素给药后4小时、12小时或24小时进行静脉穿刺、支气管镜检查和支气管肺泡灌洗（BAL）。
左氧氟沙星和环丙沙星的平均血浆浓度与先前报道的相似。对于每日一次服用500mg左氧氟沙星，ELF在4小时、12小时和24小时的平均（±标准差）稳态浓度分别为9.9±2.7μg/mL、6.5±2.5μg/mL和0.7±0.4μg/mL；AM浓度分别为97.9±80.0μg/mL、36.7±23.4μg/mL和13.8±16.0μg/mL。对于750mg左氧氟沙星，ELF的平均稳态浓度分别为22.1±14.9μg/mL、9.2±5.3μg/mL和1.5±0.8μg/mL；AM浓度分别为105.1±65.5μg/mL、36.2±26.1μg/mL和15.1±2.0μg/mL。环丙沙星在ELF中4小时和12小时的浓度分别为1.9±0.9μg/mL和0.4±0.1μg/mL；AM浓度分别为34.9±23.2μg/mL和6.8±5.9μg/mL。在每个采样时间，两个左氧氟沙星组与环丙沙星组的ELF浓度差异均有统计学意义（p<0.05）。
与环丙沙星相比，左氧氟沙星在肺内各腔室中的分布更广泛，在给药后24小时内血浆和ELF中的稳态浓度显著更高。
