TONSILLAR TISSUE PENETRATION OF DIRITHROMYCIN AFTER MULTIPLE DOSES

Dirithromycin is a new macrolide antibiotic that is effective against group A beta-hemolytic streptococcal pharyngotonsillitis. This prospec tive, multicenter, randomized study compared the serum and tonsil tiss ue concentrations of erythromycylamine (to which dirithromycin is rapi dly converted by nonenzymatic hydrolysis during absorption) and erythr omycin after 5- and 10-day regimens of dirithromycin and erythromycin, respectively. Thirty-nine patients undergoing elective tonsillectomy but without active tonsillitis were assigned in randomized fashion to receive dirithromycin 500 mg orally once daily (n = 22) or erythromyci n base 250 mg orally four times daily (n = 17). Data from 12 patients receiving dirithromycin and 10 receiving erythromycin were eligible fo r analysis. Mean serum concentrations (+/- standard deviation) of eryt hromycylamine and erythromycin were 0.20 +/- 0.07 mu g/mL and 0.12 +/- 0.25 mu g/mL, respectively, after the 5-day regimen and 0.17 +/- 0.10 mu g/mL and 1.57 +/- 3.16 mu g/mL, respectively, after the 10-day reg imen. The mean serum concentration of erythromycin after 10 days was s kewed by the data for one of the six patients in the group (concentrat ion of >8 mu g/mL), Mean concentrations of erythromycylamine in tonsil tissue were 4.62 +/- 0.97 mu g/g after 5 days and 3.47 +/- 2.84 mu g/ g after 10 days. Concentrations in tonsillar tissue were undetectable in all patients given erythromycin for 5 days and in 4 of the 6 patien ts given erythromycin for 10 days. The high concentrations of erythrom ycylamine in tonsillar tissue agree with the clinical efficacy seen in the treatment of group A beta-hemolytic streptococcal tonsillopharyng itis with dirithromycin.