Bronchopulmonary disposition of the ketolide telithromycin (HMR 3647)

Telithromycin (HMR 3647) is the first member of a new family of antimicrobi als, the ketolides, developed specifically for the treatment of community-a cquired respiratory tract infections. Telithromycin has proven in vitro act ivity against both common and atypical respiratory tract pathogens. The pen etration of telithromycin into bronchopulmonary tissues and subsequent elim ination 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 br onchoscopy and bronchoalveolar lavage 2, 8, 24, and 48 h after receipt of t he last dose, respectively. The concentration of telithromycin in the alveo lar macrophages, epithelial lining fluid (ELF), and plasma was determined b y the agar diffusion method with Bacillus subtilis ATCC 6633 as the test or ganism. The concentration of telithromycin in alveolar macrophages markedly exceeded that in plasma, reaching up to 146 times the concentration in pla sma 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 conce ntration, 2.15 mg/liter). Telithromycin median concentrations in ELF also m arkedly exceeded concentrations in plasma (median concentration in ELF, 3.7 mg/liter 8 h after dosing). Telithromycin achieves high and sustained conc entrations 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 eith er common or atypical, including intracellular, respiratory tract pathogens .