INFLUENCE OF FLUCONAZOLE ON ANTIPYRINE KINETICS IN RATS

The present study was undertaken to examine the effect of fluconazole on in vivo drug metabolism in rats, using the model substrate antipyri ne. Oral doses of fluconazole, 20 mg/kg, were administered once (acute ly) or twice daily for 4 days (chronically). Control animals received oral drug vehicle. Antipyrine kinetics were determined following an in travenous dose of 20 mg/kg given either 1 or 12 h after the single or last dose of fluconazole respectively. Acute fluconazole treatment sig nificantly increased antipyrine half-life by 250% and reduced its clea rance by 50%, without affecting its volume of distribution. Chronic tr eatment with fluconazole failed to affect antipyrine pharmacokinetics. This study demonstrates that acute fluconazole inhibits the metabolis m of antipyrine in rats.