Pulmonary disposition of lomefloxacin in patients with acute exacerbation of chronic obstructive pulmonary disease. A multiple-dose study

In this study we have measured the concentrations of lomefloxacin at steady state in serum and in the intrapulmonary region at specified intervals for 24 h following administration of the last dose of drug in patients sufferi ng from acute exacerbation of chronic obstructive pulmonary disease (COPD). Twenty subjects were enrolled. They received lomefloxacin 400 mg orally on ce-daily for 5 consecutive days. All patients were divided into five groups , with 4 subjects in each group, according to sampling times (2, 4, 8, 12, and 24 h after the last dose). At bronchoscopy, bronchial biopsies and bron choalveolar lavage (BAL) were performed. At 12 h after the last dose, serum concentration of lomefloxacin was >1.0 mug/mL and at 24 h it was still det ectable, but, at all times, the concentrations in bronchial secretion, bron chial mucosa, and epithelial lining fluid (ELF) were greater than the conce ntrations in serum [bronchial secretions (mug/mL) = 2.5 +/- 1.2; 2.2 +/- 1. 0: 2.0 +/- +/- 1.1; 1.8 +/- 1.1; 0.6 +/- 0.3. bronchial mucosa (mug/g) = 5. 9 +/- 2.1; 6.2 +/- 1.8; 2.6 +/- 2.2; 1.9 +/- 1.5; 1.0 +/- 0.9. ELF (mug/mL) = 6.9 =/- 2.8; 5.9 +/- 2.6; 3.1 +/- 1.9; 2.2 +/- 1.0; 0.8 +/- 1.3. serum ( mug/mL) = 3.2 +/- 1.4; 2.8 +/- 0.9: 2.1 +/- 1.5; 1.2 +/- 1.1; 0.4 +/- 0.8]. We must stress that we observed a large inter-individual variability in co ncentrations. Our data show that lomefloxacin once-daily induces high and s ustained concentrations in the various potential sites of pulmonary infecti on and clearly indicate that the pharmacokinetic behavior of this fluoroqui nolone permits once-daily administration in patients with acute exacerbatio ns of COPD.