Lack of an effect of azithromycin on the disposition of zidovudine and dideoxyinosine in HIV-infected patients

Two studies were conducted in HN-infected subjects to assess the potential for azithromycin to interact with zidovudine and dideoxyinosine. Both studi es used 12 subjects. The zidovudine study dosed subjects with 1200 mg/day o f azithromycin (n = 7) (later changed to 600 mg/day [n = 5]) for Days 8 to 21 of a 21-day course of 100 mg, five times/day of zidovudine. Subjects tre ated with 200 mg of dideoxyinosine twice daily for 21 days received 1200 mg of azithromycin or an equivalent amount of placebo/day for Days 8 to 21. A ntiretroviral plasma and urine sampling were conducted on Days 1, 7 and 22 for zidovudine and on Days 7 and 21 for dideoxyinosine. Peripheral mononucl ear cells were also collected for quantitation of phosphorylated zidovudine . Azithromycin had no significant impact on the C-max and AUC of zidovudine , although it significantly decreased the zidovudine t(max) by 44% and incr eased the intracellular exposure to phosphorylated zidovudine by 110%. Azit hromycin had no significant effect on dideoxyinosine pharmacokinetics. Base d on the results of these studies, it is concluded that azithromycin may be safely coadministered with both zidovudine and dideoxyinosine. (C) 2001 th e American College of Clinical Pharmacology.