Effect of Rifabutin on the Pharmacokinetics of Zidovudine in Patients Infected with Human Immunodeficiency Virus

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Abstract
We investigated the effects of rifabutin (300 tng daily administered for 7 or 14 days) on the pharmacokinetics of zidovudine in nine patients who were infected with human immunodeficiency virus (HIV). Serial blood and urine samples were collected over a 6-hour period on each day that the pharmacokinetics of zidovudine were studied. Pharmacokinetic parameters were determined for zidovudine and its glucuronide metabolite and compared with use of analysis of variance (ANOVA) appropriate for a repeated-measures design. Except for a statistically significant decrease (28%) in the terminal half-life of zidovudine from 1.5 to 1.1 hours (P = .005) after coadministration of both agents for 14 days, concurrent administration of rifabutin for 7 or 14 days had no statistically significant effects on zidovudine plasma and urine pharmacokinetic parameters (the difference among treatment means was <25%). Treatment with rifabutin is unlikely to influence the effectiveness of treating HIV-infected patients with zidovudine because of any pharmacokinetic interaction between these drugs.

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