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 antipyrine. Oral doses of fluconazole, 20 mg/kg, were administered once (acutely) or twice daily for 4 days (chronically). Control animals received oral drug vehicle. Antipyrine kinetics were determined following an intravenous dose of 20 mg/kg given either 1 or 12 h after the single or last dose of fluconazole respectively. Acute fluconazole treatment significantly increased antipyrine half-life by 250% and reduced its clearance by 50%, without affecting its volume of distribution. Chronic treatment with fluconazole failed to affect antipyrine pharmacokinetics. This study demonstrates that acute fluconazole inhibits the metabolism of antipyrine in rats.
Ramzan
I
I
Department of Pharmacy, University of Sydney, Australia.
Chan
M
M
D000284:Administration, Oral; D000818:Animals; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015725:Fluconazole; D000983:Antipyrine