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

Autor:	K Gallicano, Jan Sahai, A Pakuts, D. W. Cameron
Rok vydání:	1994
Předmět:	Adult Male Analysis of Variance business.industry HIV Infections Urine Pharmacology Drug interaction Crossover study Zidovudine Infectious Diseases Therapeutic index Pharmacokinetics Humans Immunology and Allergy Medicine Drug Therapy Combination Adverse effect business Fluconazole medicine.drug
Zdroj:	Scopus-Elsevier
ISSN:	1537-6613 0022-1899
DOI:	10.1093/infdis/169.5.1103
Popis:	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.
Databáze:	OpenAIRE
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