Pharmacokinetics of gatifloxacin after a single oral dose in healthy young adult subjects and adult patients with chronic bronchitis, with a comparison of drug concentrations obtained by bronchoscopic microsampling and bronchoalveolar lavage

Abstract

Background: Bronchoalveolar lavage (BAL) is an established technique for measuring antibiotic concentrations in the epithelial lining fluid (ELF) of the bronchiolar and alveolar regions; however, the results may not reflect concentrations in bronchial regions. Bronchoscopic microsampling (BMS) is a technique that makes it possible to obtain multiple samples from bronchial ELF. Objective: BMS and BAL were used to analyze the pharmacokinetics of gatifloxacin in bronchial ELF from healthy young adult subjects and adult patients with chronic bronchitis. Methods: Bronchial ELF samples were obtained by BMS at 1, 2, 3, 4, 6, 10, and 24 hours after administration of a single oral dose of gatifloxacin 200 mg in healthy young adult (aged 20–25 years) subjects, and at 1, 2, 4, and 10 hours after a single dose in patients with chronic bronchitis (aged ≥20 years). At least 1 month after the initial BMS, alveolar (BAL) and bronchial (BMS) ELF samples were obtained from another group of healthy subjects 2 hours after administration of a single oral dose of gatifloxacin 200 mg for comparison of gatifloxacin concentrations in samples obtained by the 2 techniques. Results: Bronchial ELF samples were obtained from 8 healthy subjects and 5 patients with chronic bronchitis; alveolar ELF samples were obtained from a separate group of 5 healthy subjects. For the healthy subjects, the mean (SD) AUC 0–24 in serum and bronchial ELF, corrected for mg/kg doses, was 4.6 (1.1) and 7.6 (3.5) mg · h/L, respectively. In the patients with chronic bronchitis, the AUC 0–10 in serum and bronchial ELF, corrected for mg/kg doses, was 3.9 (0.8) and 4.1 (1.5) mg · h/L. The C max in serum and bronchial ELF, corrected for mg/kg doses, was 0.6 (0.2) and 1.4 (0.8) mg/L in healthy subjects and 0.7 (0.2) and 0.7 (0.2) mg/L in patients with chronic bronchitis. In healthy subjects, the C max and AUC 0–24 were significantly higher in bronchial ELF than in serum (both, P < 0.05). Gatifloxacin concentrations were significantly lower in bronchial ELF obtained by BMS than in alveolar ELF obtained by BAL ( P < 0.05). Conclusions: Based on the findings of this study in small numbers of healthy young adult volunteers and patients with chronic bronchitis, BMS appears to be a promising method for measuring drug concentrations and determining the pharmacokinetic profile of gatifloxacin in bronchial ELF. Additional studies are needed to correlate measured concentrations obtained by BMS with clinical and/or microbiologic outcomes in larger populations.