title: Bronchoscopic microsampling method for measuring drug concentration in epithelial lining fluid.
abstract: Direct measurement of the concentration of antimicrobial agents in bronchial epithelial lining fluid (ELF) would allow for a more informed approach to appropriate dosing of antimicrobial agents for respiratory tract infections. In this study, we determined the time versus concentration profile in ELF after an oral administration of levofloxacin, using recently developed bronchoscopic microsampling probes. These probes could be repeatedly and safely inserted through the fiberoptic bronchoscope in normal healthy volunteers. The concentration of levofloxacin in ELF was 43.4% of the corresponding serum value at 1 hour, reached the same level at 2 hours, decreased in a similar manner as that in serum, and returned to undetectable levels at 24 hours. It exceeded minimal inhibitory concentrations of Staphylococcus aureus (0.25 microg/ml), Klebsiella species (0.5 microg/ml), and Haemophilus influenzae (0.06 microg/ml) after 6 hours. The experimental procedure was well tolerated, and no complications were observed. In conclusion, bronchoscopic microsampling is a feasible and promising method for measuring antimicrobial concentrations in the target sites of respiratory tracts directly and repeatedly.
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, Kitaku, Sapporo, Japan. kyamazak@med.hokudai.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ogura
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Toshinari
authors.initials: T
authors.lastname: Oh-hara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001980:Bronchi / Q000378:metabolism*; D001999:Bronchoscopy / Q000379:methods*; D005240:Feasibility Studies; D006801:Humans; D064704:Levofloxacin; D008297:Male; D015242:Ofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D015203:Reproducibility of Results; D020545:Respiratory Mucosa / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin