THE LEVELS OF CLARITHROMYCIN AND ITS 14-HYDROXY METABOLITE IN THE LUNG

Clarithromycin is a new macrolide that has a longer half-life than ery thromycin and is claimed to reach higher tissue concentrations. We aim ed to investigate whether, following oral administration, the drug and its 14-hydroxy metabolite reach levels in lung tissue that are likely to be clinically effective against common respiratory pathogens. Ten patients undergoing diagnostic bronchoscopy received seven doses of cl arithromycin, 500 mg b.i.d. orally. Bronchoscopy was performed at a me an time of 4.25 h after the last dose. At bronchoscopy, bronchial biop sies and bronchoalveolar lavage were performed. Clarithromycin and its 14-OH metabolite were measured in serum, bronchial biopsies, epitheli al lining fluid (ELF) and alveolar cells Mean levels of clarithromycin were 4.0 mg.l-1 in serum, 16.8 mg.kg in bronchial biopsies, 20.5 mg.l -1 in ELF and 372.7 mg.l-1 in alveolar cells. The equivalent levels of 14-OH metabolite were 0.7, 2.7, 1.9 and 38.6 mg.l-1, respectively. We conclude that there is considerable concentration of clarithromycin a nd its 14-OH metabolite in alveolar cells, and to a lesser extent in b ronchial tissue and ELF; this implies efficacy against susceptible org anisms at these sites.