Lack of an effect of azithromycin on the disposition of zidovudine and dideoxyinosine in HIV-infected patients.
Two studies were conducted in HIV-infected subjects to assess the potential for azithromycin to interact with zidovudine and dideoxyinosine. Both studies used 12 subjects. The zidovudine study dosed subjects with 1200 mg/day of 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 treated 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. Antiretroviral plasma and urine sampling were conducted on Days 1, 7, and 21 for zidovudine and on Days 7 and 21 for dideoxyinosine. Peripheral mononuclear cells were also collected for quantitation of phosphorylated zidovudine. Azithromycin had no significant impact on the Cmax and AUC of zidovudine, although it significantly decreased the zidovudine tmax by 44% and increased the intracellular exposure to phosphorylated zidovudine by 110%. Azithromycin had no significant effect on dideoxyinosine pharmacokinetics. Based on the results of these studies, it is concluded that azithromycin may be safely coadministered with both zidovudine and dideoxyinosine.
Amsden
G
G
Clinical Pharmacology Research Center, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326, USA.
Flaherty
J
J
Luke
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000494:pharmacology*; D016049:Didanosine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015215:Zidovudine / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D015215:Zidovudine; D017963:Azithromycin; D016049:Didanosine