Dirithromycin

Abstract

Dirithromycin is a semisynthetic derivative of erythromycin, a 14-membered ring macrolide antibiotic. The drug is converted during absorption and distribution, to an active metabolite 9-( S)-erythromycylamine, which is the predominant compound found in plasma and extravascular tissues. High tissue concentration of erythromycylamine is achieved after oral doses of dirithromycin, with slow release back into the circulation. 1 The mechanism of action of dirithromycin is like that of erythromycin and other macrolides. These compounds inhibit RNA-dependent protein synthesis. 1–3 It has recently been suggested that all macrolides stimulate dissociation of peptidyl-tRNA from ribosomes during the elongation phase, leading to inhibited protein synthesis. 2 The antimicrobial spectrum of dirithromycin is similar to that of erythromycin, although the drug offers no significant advantage with regard to MIC values. In vitro against Gram-positive isolates, dirithromycin exhibits similar potency to that of clarithromycin, erythromycin, roxithromycin, and clindamycin. In vivo, dirithromycin is active against penicillin-susceptible Staphylococcus aureus, beta-hemolytic streptococci, and Streptococccus pneumoniae. Dirithromycin is as effective as penicillin VK against streptococcal pharyngitis and tonsilitis, and as effective as erythromycin against acute superimposed chronic bronchitis and skin and soft-tissue infections. In comparison with other newer macrolides, dirithromycin has shown similar or lesser in vitro activity. In particular, Haemophilus influenzae, Bacteroides spp., Peptococcus-Peptostreprococcus spp., Clostridium perfringens, Legionella spp., Neisseria gonorrhoeae, and Chlamydia trachomatis were all less sensitive to dirithromycin than azithromycin or clarithromycin. 3,4 Once-daily oral administration of dirithromycin (500 mg) has been demonstrated to be similar in efficacy to erythromycin (250 mg, 4 times daily), each for approximately 7 days, in the treatment of acute bronchitis or acute exacerbations of chronic bronchitis in controlled studies. 1,3 Proven or presumed pathogen eradication rates were 83 and 86% for acute bronchitis patients treated with dirithromycin and erythromycin, respectively. Corresponding bacteriological response rates in acute exacerbations of chronic bronchitis were 75 to 84% with dirithromycin and 75 to 82% with erythromycin. Both agents achieved clinical cure or improvement in over 85% of the patients with either condition. The main advantage of dirithromycin over erythromycin appears to be once-daily administration. Lilly launched dirithromycin in September 1993, in Spain, received approval from the FDA in August 1995, and launched it during October 1995.