Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.
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.
Sahai
J
J
Clinical Investigation Unit, Ottawa General Hospital, Canada.
Gallicano
K
K
Pakuts
A
A
Cameron
D W
DW
D000328:Adult; D000704:Analysis of Variance; D004359:Drug Therapy, Combination; D015725:Fluconazole / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D015215:Zidovudine / Q000493:pharmacokinetics* / Q000627:therapeutic use
D015215:Zidovudine; D015725:Fluconazole