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Published ahead of print on August 6, 2003, doi:10.1164/rccm.200301-111OC
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American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 1304-1307, (2003)
© 2003 American Thoracic Society

Bronchoscopic Microsampling Method for Measuring Drug Concentration in Epithelial Lining Fluid

Koichi Yamazaki, Shigeaki Ogura, Akitoshi Ishizaka, Toshinari Oh-hara and Masaharu Nishimura

First Department of Medicine, Hokkaido University School of Medicine; Department of Respiratory Disease, Sapporo City General Hospital, Sapporo; Department of Medicine, Tokyo Electric Power Company Hospital, Ibaraki; and Contract Research Department I, ADME/TOX Research Institute, Daiichi Pure Chemicals Co., Ltd., Tokyo, Japan

Correspondence and requests for reprints should be addressed to Koichi Yamazaki, First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kitaku, Sapporo 060-8638, Japan. E-mail: kyamazak{at}med.hokudai.ac.jp

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 µg/ml), Klebsiella species (0.5 µg/ml), and Haemophilus influenzae (0.06 µg/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.

Key Words: bronchoscopy • antimicrobial agents • respiratory tract infection • time versus concentration profile • levofloxacin




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