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Published ahead of print on August 6, 2003, doi:10.1164/rccm.200301-111OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 11, December 2003, 1304-1307

A more recent version of this article appeared on December 1, 2003
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Submitted on February 5, 2003
Accepted on August 4, 2003

Bronchoscopic microsampling method for measuring drug concentration in epithelial lining fluid

Koichi Yamazaki1*, Shigeaki Ogura2, Akitoshi Ishizaka3, Toshinari Oh-hara4, and Masaharu Nishimura1

1 First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan, 2 Respiratory Disease, Sapporo City General Hospital, Sapporo, Japan; First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan, 3 Medicine, Tokyo Electric Power Company Hospital, Tokyo, Japan, 4 Contract Research Department I, ADME/TOX Research Institute, Daiichi Pure Chemicals Co., Ltd., Tokyo, Japan

* To whom correspondence should be addressed. 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 (BMS) 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 h, reached the same level at 2 h, decreased in a similar manner as that in serum and returned to undetectable levels at 24 h. 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 h. The experimental procedure was well tolerated and no complications were observed. In conclusion, BMS 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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