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 lining fluid (ELF) and serum in 25 patients with acute exacerbation of chronic bronchitis after a 5-day, once-daily, dirithromycin 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 microgram/ml at 24 h, 0.31 microgram/ml at 48 h, 0.33 microgram/ml at 72 h, 0.12 microgram/ml at 96 h and 0.11 microgram/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 micrograms/ml, respectively, in BS; 2.59, 2.59, 1.96, 0.41 and 0.27 micrograms/g, respectively, in BM; 2.21, 2.25, 1.57, 0.22 and 0.15 micrograms/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.
Cazzola
M
M
Istituto di Farmacologia e Tossicologia, Facoltà di Medicina e Chirurgia, Seconda Università Napoletana, Napoli, Italy.
Matera
M G
MG
Tufano
M A
MA
Polverino
M
M
Catalanotti
P
P
Varanese
L
L
Rossi
F
F
D000900:Anti-Bacterial Agents; D001980:Bronchi / Q000378:metabolism; D001991:Bronchitis / Q000378:metabolism* / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D002908:Chronic Disease; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000378:metabolism*; D018942:Macrolides; D001936:Moraxella catarrhalis / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000900:Anti-Bacterial Agents; D018942:Macrolides; C053853:dirithromycin; D004917:Erythromycin