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JAC Advance Access published online on March 10, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki034
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JAC © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Received September 20, 2004
Revised November 24, 2004
Accepted December 27, 2004

Brief report

Penetration of telithromycin into the nasal mucosa and ethmoid bone of patients undergoing rhinosurgery for chronic sinusitis

T. S. Kuehnel 1*, C. Schurr 1, K. Lotter 2, and F. Kees 2

1 Departments of Otolaryngology, Head and Neck Surgery, Regensburg, Germany and
2 Department of Pharmacology, University of Regensburg, D-93053 Regensburg, Germany

* To whom correspondence should be addressed.
T. S. Kuehnel, E-mail: Thomas.Kuehnel{at}klinik.uni-regensburg.de


  Abstract

Objectives: Telithromycin has a broad spectrum of activity against respiratory tract pathogens including penicillin- and macrolide-resistant streptococci. The aim of the study was to investigate the penetration of telithromycin into nasal tissue following a single oral dose of 800 mg.

Patients and methods: A total of 29 patients undergoing rhinosurgery for chronic sinusitis were evaluated. Samples of blood, nasal mucus, nasal mucosa and ethmoid bone were collected during surgery in groups of 5-6 patients after 3, 6, 9, 15 and 24 h following a single oral dose of 800 mg telithromycin. Drug concentrations were determined by HPLC with fluorimetric detection.

Results: The highest telithromycin concentrations were observed after 3 h in plasma as well as in all tissues sampled. The mean plasma concentrations were 0.73 mg/L in the 3 h group and 0.02 mg/L in the 24 h group. The concomitant tissue concentrations were higher. The tissue penetration, expressed by the ratio of the area under the concentration-time curve in tissue versus plasma, was 1.0 for nasal mucus, 5.9 for nasal mucosa and 1.6 for ethmoid bone.

Conclusions: Telithromycin achieved tissue concentrations that were generally above the MIC90 for common pathogens in upper respiratory tract infections. These results indicate that telithromycin diffuses rapidly into the nasal tissues and achieves high and prolonged concentrations in nasal mucosa and ethmoid bone.

Keywords: ketolides; pharmacokinetics; nasal tissue.
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