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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.

AbstractBACKGROUND:
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.
AuthorsJunko Kikuchi, Koichi Yamazaki, Eiki Kikuchi, Akitoshi Ishizaka, Masaharu Nishimura
JournalClinical therapeutics (Clin Ther) Vol. 29 Issue 1 Pg. 123-30 (Jan 2007) ISSN: 0149-2918 [Print] United States
PMID17379052 (Publication Type: Clinical Trial, Comparative Study, Journal Article)
Chemical References
  • Anti-Infective Agents
  • Fluoroquinolones
  • gatifloxacin
Topics
  • Administration, Oral
  • Adult
  • Aged
  • Anti-Infective Agents (pharmacokinetics, therapeutic use)
  • Area Under Curve
  • Bronchitis, Chronic (drug therapy)
  • Bronchoalveolar Lavage (methods)
  • Bronchoalveolar Lavage Fluid (chemistry)
  • Bronchoscopy (methods)
  • Chromatography, High Pressure Liquid
  • Fluoroquinolones (pharmacokinetics, therapeutic use)
  • Humans
  • Middle Aged
  • Specimen Handling

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