Pulmonary Disposition of Lomefloxacin in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. A Multiple-Dose Study

Abstract

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 suffering from acute exacerbation of chronic obstructive pulmonary disease (COPD). Twenty subjects were enrolled. They received lomefloxacin 400 mg orally once-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 bron-choscopy, bronchial biopsies and bronchoalveolar lavage (BAL) were performed. At 12 h after the last dose, serum concentration of lomefloxacin was >1.0 μg/mL and at 24 h it was still detectable, but, at all times, the concentrations in bronchial secretion, bronchial mucosa, and epithelial lining fluid (ELF) were greater than the concentrations in serum [bronchial secretions (μg/mL) = 2.5 ± 1.2; 2.2 ± 1.0: 2.0 ±1.1; 1.8 ± 1.1; 0.6 ± 0.3. bronchial mucosa (μg/g) = 5.9 ± 2.1; 6.2 ± 1.8; 2.6 ± 2.2; 1.9 ± 1.5; 1.0 ± 0.9. ELF (μg/mL) = 6.9 ± 2.8; 5.9 ± 2.6; 3.1 ± 1.9; 2.2 ± 1.0; 0.8 ± 1.3. serum (μg/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 concentrations. Our data show that lomefloxacin once-daily induces high and sustained concentrations in the various potential sites of pulmonary infection and clearly indicate that the pharmacokinetic behavior of this fluoroquinolone permits once-daily administration in patients with acute exacerbations of COPD.