COMPARISON OF AZITHROMYCIN AND CLARITHROMYCIN IN THEIR INTERACTIONS WITH RIFABUTIN IN HEALTHY-VOLUNTEERS

A 14-day, randomized, open, phase I clinical trial was designed to exa mine possible pharmacokinetic interactions between rifabutin and two o ther antibiotics, azithromycin and clarithromycin, used in the treatme nt of Mycobacterium avium complex infections. Thirty healthy male and female volunteers were divided into five groups of six participants ea ch: 18 received 300 mg/day of rifabutin, 12 in combination with therap eutic doses of either azithromycin or clarithromycin; the remaining 12 received azithromycin or clarithromycin alone. On day 10 the study wa s terminated because of adverse events, including severe neutropenia. Fourteen participants who received rifabutin developed neutropenia, in cluding all 12 participants Mho received azithromycin or clarithromyci n concomitantly. Analyses of serum revealed no apparent pharmacokineti c interaction between azithromycin and rifabutin. However, the mean co ncentrations of rifabutin and 25-O-desacetyl-rifabutin (an active meta bolite) in participants who received clarithromycin and rifabutin conc omitantly were more than 400% and 3,700%, respectively, of concentrati ons in those who received rifabutin alone. Physicians should be aware that recommended prophylactic doses of rifabutin may be associated wit h severe neutropenia within 2 weeks after initiation of therapy, and a ll patients receiving rifabutin, especially with clarithromycin, shoul d be monitored carefully for neutropenia. Journal of Clinical Pharmaco logy, 1998;38:830-835 (C) 1998 The American College of Clinical Pharma cology.