title: The levels of clarithromycin and its 14-hydroxy metabolite in the lung.
abstract: Clarithromycin is a new macrolide that has a longer half-life than erythromycin and is claimed to reach higher tissue concentrations. We aimed 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 clarithromycin, 500 mg b.i.d. orally. Bronchoscopy was performed at a mean time of 4.25 h after the last dose. At bronchoscopy, bronchial biopsies and bronchoalveolar lavage were performed. Clarithromycin and its 14-OH metabolite were measured in serum, bronchial biopsies, epithelial 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 and its 14-OH metabolite in alveolar cells, and to a lesser extent in bronchial tissue and ELF; this implies efficacy against susceptible organisms at these sites.
authors.affiliation: Dept of Thoracic Medicine, Dudley Road Hospital, Birmingham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Honeybourne
authors.forename: F
authors.initials: F
authors.lastname: Kees
authors.forename: J M
authors.initials: JM
authors.lastname: Andrews
authors.forename: D
authors.initials: D
authors.lastname: Baldwin
authors.forename: R
authors.initials: R
authors.lastname: Wise
mesh_terms: D017291:Clarithromycin / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male
chemical_list: D017291:Clarithromycin