DIRITHROMYCIN CONCENTRATIONS IN BRONCHIAL-MUCOSA AND SECRETIONS

Since a high tissue penetration of dirithromycin (D) has been assessed in early studies, the aims of this study were to determine D concentr ations in bronchial mucosa and secretions in patients suffering from a n acute exacerbation of chronic bronchitis (AECB), to compare intra-in dividual bronchial mucosa and secretion concentrations and to relate b ronchial concentrations of D and clinical efficacy. The main inclusion criteria were comprised of (1) AECB, defined by the presence of an in crease in dyspnea, sputum production and change in sputum purulence, a nd (2) clinical indication of fiberoptic bronchoscopy allowing perform ance of bronchial biopsies. All patients were treated with a 500-mg on ce-daily D dose for 5 days. Patients were randomly divided into three groups, according to sampling times (24, 48 and 72 h after the last do se). Tissue concentration analyses were performed by one blinded micro biologist (microbiological agar diffusion assay). The results showed: (1) 37 out of the 46 patients (80.4%) had a favorable response to trea tment at the time of fiberoptic bronchoscopy (14 cured, 23 improved); (2) bronchial mucosa concentrations were high in all groups, and (3) m ean values at 24, 48 and 72 h after the last dose were respectively 6. 51 +/- 1.44, 6.61 +/- 2.7, 5.67 +/- 1.02 mg.kg(-1); no statistical dif ference was observed between the groups. In bronchial secretions colle cted simultaneously, concentrations were lower, i.e. 1.26 +/- 0.3, 0.6 1 +/- 0.12, 0.84 +/- 0.12. Significant associations were observed betw een bronchial mucosa and secretion concentrations (r = 0.71, p = 0.000 1), and between clinical response and bronchial concentrations (p = 0. 03, Kruskall-Wallis test). In conclusion, these results may confirm th e clinical significance of tissue concentrations measured in bronchial tissues of patients with AECB.