Dirithromycin concentrations in bronchial mucosa and secretions

Area of Science:

• Pharmacology
• Respiratory Medicine
• Infectious Diseases

Background:

• Dirithromycin (D) has demonstrated high tissue penetration in previous studies.
• Acute exacerbation of chronic bronchitis (AECB) requires effective antibiotic treatment with good drug penetration to target sites.

Purpose of the Study:

• To quantify dirithromycin concentrations in bronchial mucosa and secretions in AECB patients.
• To compare drug levels between bronchial mucosa and secretions.
• To correlate dirithromycin concentrations with clinical efficacy in AECB.

Main Methods:

• 46 patients with AECB underwent fiberoptic bronchoscopy for bronchial biopsies and secretion collection.
• Patients received a 500-mg daily dose of dirithromycin for 5 days.
• Bronchial tissue and secretion concentrations were measured using microbiological agar diffusion assays at 24, 48, and 72 hours post-treatment.

Main Results:

• 80.4% of patients showed a favorable clinical response (14 cured, 23 improved).
• High dirithromycin concentrations were found in bronchial mucosa (mean 5.67-6.61 mg/kg) across all sampling times.
• Bronchial secretion concentrations were significantly lower than mucosal concentrations, but correlated significantly with mucosal levels (r=0.71).
• A significant association was observed between higher bronchial dirithromycin concentrations and improved clinical response (p=0.03).

Conclusions:

• Dirithromycin achieves high concentrations in bronchial mucosa of AECB patients.
• Bronchial mucosa concentrations, not secretion levels, are significantly associated with clinical outcomes.
• These findings support the clinical relevance of measuring dirithromycin tissue concentrations in the bronchial mucosa for AECB treatment.