Bronchopulmonary pharmacokinetic and pharmacodynamic profiles of levofloxacin 750 mg once daily in adults undergoing treatment for acute exacerbation of chronic bronchitis.

While previous reports have described the bronchopulmonary profile of the fluoroquinolones in healthy volunteers, limited data are available in infected patients. The purpose of this study was to determine the intrapulmonary profile of high-dose (750 mg) levofloxacin in patients during an acute exacerbation of chronic bronchitis (AECB). Twenty-four patients experiencing clinical signs and symptoms of AECB were enrolled. Once enrolled, patients received levofloxacin 750 mg once daily × 5 days. Bronchoalveolar lavage aspirates and simultaneous plasma samples were obtained at 4 h, 12 h or 24 h after the third dose. Concentrations in biologic matrixes were determined with a validated HPLC method. Epithelial lining fluid (ELF) concentrations were calculated using the urea dilution method. Five patients did not complete the trial, 19 patients underwent bronchoscopy, 18 (52 ± 13 yrs) had sufficient samples for analysis and confirmed medication compliance. Mean plasma concentrations at 4, 12, and 24 h were 8.0 ± 2.5, 5.8 ± 1.2, and 2.2 ± 1.2 μg/mL. Mean ELF values at 4, 12, and 24 h were 7.5 ± 3.0, 8.3 ± 6.0, and 1.2 ± 0.9 μg/mL. Mean alveolar macrophage (AM) concentrations at 4, 12, and 24 h were 38.5 ± 43.7, 13.4 ± 14.4, and 9.0 ± 7.5 μg/mL. The penetration (ELF/plasma ratio) into the infection site was 113%. In these subjects with AECB, levofloxacin 750 mg once daily reached adequate exposures in the plasma, ELF, and AMs for the most commonly associated pathogens.