PULMONARY PENETRATION OF DIRITHROMYCIN IN PATIENTS SUFFERING FROM ACUTE EXACERBATION OF CHRONIC-BRONCHITIS

The aim of this study was to evaluate the concentrations of dirithromycin, a new macrolide antibiotic, in bronchial secretions (BS), bronchial mucosa (BM), epithelial liming fluid (ELF) and serum in 25 patients with acute exacerbation of chronic bronchitis after a 5-day, once-daily, diritromycin regimen. All patients received dirithromycin, 500 mg (two 250 mg tablets) given orally once daily at 08.00 fasted, for 5 consecutive days. They were divided into five groups (n = 5 in each group) according to sampling time (24, 48, 72, 96 and 120 h after the last dose). Mean serum concentrations remained low throughout the study (0.44 mu g/ml at 24 h, 0.31 mu g/ml at 48 h, 0.33 mu g/ml at 72 h, 0.12 mu g/ml at 96 h and 0.11 mu g/ml at 120 h, respectively), although they were higher than the MICs for Moraxella catarrhalis for up to 72 h and than that for Streptococcus pneumoniae for up to 120 h after the last dose. By contrast, in all other samples, mean concentrations were higher than the MICs for many relevant respiratory pathogens for at least 3 days, and higher than that for S. pneumonia and M. catarrhalis for up to 120 h (mean concentrations measured 2.67, 2.15, 1.74, 0.27 and 0.17 mu g/ml, respectively, in BS; 2.59, 2.59, 1.96, 0.41 and 0.27 mu g/g, respectively, in BM; 2.21, 2.25, 1.57, 0.22 and 0.15 mu g/ml, respectively, in ELF). These findings demonstrate that dirithromycin is concentrated in each of these potential sites of infection for up to 3 days after a 5-day course of therapy. Therefore, short-term therapy with dirithromycin may be useful for many respiratory infections.