Pulmonary concentrations of dirithromycin and erythromycin during acute exacerbation of mild chronic obstructive pulmonary disease.

Abstract

We compared the concentrations of dirithromycin and erythromycin at steady state in serum and the intrapulmonary region in patients suffering from acute exacerbation of mild chronic obstructive pulmonary disease. Twenty patients received dirithromycin, 500 mg given orally once daily for five consecutive days. The other 20 patients were treated with erythromycin base, which was administered orally four times daily at a total daily dose of 1000 mg for seven days. All patients were divided into eight groups, with five subjects in each group, according to sampling times (2, 4, 8, and hrs after the last dose) and treatment. After the erythromycin treatment mean serum concentrations were higher than those of dirithromycin treatment mean serum concentrations were higher than those of dirithromycin for upto 4 hours, but they were undetectable 24 hours after the last dose. At all time periods, the concentrations of dirithromycin in bronchial secretion, bronchial mucosa and epithelial lining fluid were greater than the concentration in serum. Concentrations of erythromycin were always lower than those of dirithromycin in the explored pulmonary sites. Our data demonstrated that a five day course of 500 mg of dirithromycin once daily induced higher concentrations and longer persistence in the various potential sites of pulmonary infection than a seven day course of 250 mg of erythromycin every 6 hrs. The shorter duration of therapy and the once daily dosing with good efficacy against common respiratory pathogens would be advantageous for patients and would be likely to promote better patient compliance and acceptability.