Pharmacokinetics of telithromycin using bronchoscopic microsampling after single and multiple oral doses.
OBJECTIVE
Bronchoscopic microsampling (BMS) is a new technique for repeated sampling of bronchial epithelial lining fluid (ELF) to obtain the pharmacokinetic profile of drugs. We analyzed the time versus concentration profiles of telithromycin in bronchial ELF obtained by BMS and compared these finding to those in plasma and alveolar ELF obtained by bronchoalveolar lavage (BAL).


METHODS
Bronchial ELF samples were obtained from five healthy subjects using BMS probe at 0, 2, 3, 4, 6, 10 and 24h after single or multiple oral doses of 600 mg of telithromycin. Alveolar ELF was also obtained by BAL 3h after single or multiple oral doses of 600 mg of telithromycin.


RESULTS
The areas under the concentration-time curve from 0 to 24h (AUC0-24) of telithromycin in plasma and bronchial ELF were 2.86+/-0.60 and 19.5+/-10.4 mg h/l after single treatment and 3.60+/-0.49 and 42.2+/-22.7 mg h/l after multiple treatments, respectively. Single and multiple oral doses of telithromycin produced significantly (p<0.05) higher AUC0-24 in bronchial ELF compared to those in plasma. While concentrations in bronchial ELF obtained by BMS were significantly lower than those in alveolar ELF obtained by BAL, they tended to be higher than those in plasma after multiple administration. The telithromycin concentrations obtained by BMS method were very consistent in bronchial ELF at different bronchi at one time point and at the same bronchus at different time points.


CONCLUSIONS
Using the BMS technique, we could describe the pharmacokinetics of telithromycin in bronchial ELF. Furthermore, BMS was reasonably validated and reconfirmed to be a feasible and reliable method for measuring antimicrobial concentrations in bronchial ELF.
Kikuchi
Junko
J
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Yamazaki
Koichi
K
Kikuchi
Eiki
E
Ishizaka
Akitoshi
A
Nishimura
Masaharu
M
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001980:Bronchi / Q000378:metabolism; D018893:Bronchoalveolar Lavage / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy / Q000379:methods*; D004334:Drug Administration Schedule; D006801:Humans; D048628:Ketolides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D013048:Specimen Handling; D013997:Time Factors; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D048628:Ketolides; C106791:telithromycin