Document 0087
 DOCN  M9460087
 TI    Effect of fluconazole on zidovudine pharmacokinetics in patients
       infected with human immunodeficiency virus.
 DT    9408
 AU    Sahai J; Gallicano K; Pakuts A; Cameron DW; Clinical Investigation Unit,
       Ottawa General Hospital, Canada.
 SO    J Infect Dis. 1994 May;169(5):1103-7. Unique Identifier : AIDSLINE
       MED/94223072
 AB    The effect of a therapeutic dose of fluconazole on the disposition of
       zidovudine was evaluated in 12 men infected with human immunodeficiency
       virus. The study was designed as a randomized, two-period,
       two-treatment, crossover trial. On two occasions, 21 days apart,
       patients received either zidovudine alone or zidovudine (each, 200 mg
       every 8 h) and fluconazole (400 mg daily) for 7 days. Fluconazole
       coadministration decreased (P < .001) the apparent oral serum clearance
       of zidovudine by 43% and the apparent oral formation clearance to
       zidovudine glucuronide (GZDV) by 48%, resulting in increases (P < .002)
       in the area under the serum concentration time curve (74%), the maximum
       serum concentration (84%), and the terminal half-life (128%) of
       zidovudine. The molar ratio of GZDV to zidovudine recovered in urine was
       reduced by 34% with fluconazole (P < .001). These pharmacokinetic
       changes suggest that 400 mg of fluconazole inhibited the conversion of
       zidovudine to GZDV. Patients receiving this combination should be
       monitored for the development of zidovudine-related adverse reactions.
 DE    Adult  Analysis of Variance  Drug Therapy, Combination
       Fluconazole/*THERAPEUTIC USE  Human  HIV Infections/*DRUG THERAPY  Male
       Support, Non-U.S. Gov't  Zidovudine/*PHARMACOKINETICS/THERAPEUTIC USE
       CLINICAL TRIAL  JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).