title: 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 > or =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 x 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 x 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.
authors: First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan. johmuro@med.hokudai.ac.jp
authors: Junko
authors: J
authors: Kikuchi
authors: Koichi
authors: K
authors: Yamazaki
authors: Eiki
authors: E
authors: Kikuchi
authors: Akitoshi
authors: A
authors: Ishizaka
authors: Masaharu
authors: M
authors: Nishimura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D029481:Bronchitis, Chronic / Q000188:drug therapy*; D018893:Bronchoalveolar Lavage / Q000379:methods*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D024841:Fluoroquinolones / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077734:Gatifloxacin; D006801:Humans; D008875:Middle Aged; D013048:Specimen Handling
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D000077734:Gatifloxacin