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Antimicrobial Agents and Chemotherapy, November 2001, p. 3104-3108, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.3104-3108.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Bronchopulmonary Disposition of the Ketolide Telithromycin (HMR 3647)

Claudette Muller-Serieys,1,* Paul Soler,2 Cathy Cantalloube,3 Françoise Lemaitre,1 Hai Pham Gia,3 Françoise Brunner,3 and Antoine Andremont1

Unité de Microbiologie, Hôpital Bichat-Claude Bernard, 75877 Paris,1 INSERM U-408, UFR Xavier Bichat, 75018 Paris,2 and Aventis Pharma, 93235 Romainville Cedex,3 France

Received 18 September 2000/Returned for modification 27 February 2001/Accepted 26 July 2001

Telithromycin (HMR 3647) is the first member of a new family of antimicrobials, the ketolides, developed specifically for the treatment of community-acquired respiratory tract infections. Telithromycin has proven in vitro activity against both common and atypical respiratory tract pathogens. The penetration of telithromycin into bronchopulmonary tissues and subsequent elimination from these sites were evaluated in four groups (groups A, B, C, and D) of six healthy male subjects who received telithromycin at 800 mg once daily for 5 days. Subjects in groups A, B, C, and D underwent fiberoptic bronchoscopy and bronchoalveolar lavage 2, 8, 24, and 48 h after receipt of the last dose, respectively. The concentration of telithromycin in the alveolar macrophages, epithelial lining fluid (ELF), and plasma was determined by the agar diffusion method with Bacillus subtilis ATCC 6633 as the test organism. The concentration of telithromycin in alveolar macrophages markedly exceeded that in plasma, reaching up to 146 times the concentration in plasma 8 h after dosing (median concentration, 81 mg/liter). Telithromycin was retained in alveolar macrophages 24 h after dosing (median concentration, 23 mg/liter), and it was still quantifiable 48 h after dosing (median concentration, 2.15 mg/liter). Telithromycin median concentrations in ELF also markedly exceeded concentrations in plasma (median concentration in ELF, 3.7 mg/liter 8 h after dosing). Telithromycin achieves high and sustained concentrations in ELF and in alveolar macrophages, while it maintains adequate levels in plasma, providing an ideal pharmacokinetic profile for effective treatment of community-acquired respiratory tract infections caused by either common or atypical, including intracellular, respiratory tract pathogens.

* Corresponding author. Mailing address: Unité de Microbiologie, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75877 Paris, France. Phone: 33 (1) 40 25 80 80. Fax: 33 (1) 40 25 88 52. E-mail: claudette.muller{at}bch.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, November 2001, p. 3104-3108, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.3104-3108.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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