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Diflucan - Clinical Pharmacology

[Fluconazole]



Zidovudine

Plasma zidovudine concentrations were determined on two occasions (before and following fluconazole 200 mg daily for 15 days) in 13 volunteers with AIDS or ARC who were on a stable zidovudine dose for at least two weeks. There was a significant increase in zidovudine AUC following the administration of fluconazole. The mean ± SD increase in AUC was 20% ± 32% (range: ?27 to 104%). The metabolite, GZDV, to parent drug ratio significantly decreased after the administration of fluconazole, from 7.6 ± 3.6 to 5.7 ± 2.2.

Theophylline

The pharmacokinetics of theophylline were determined from a single intravenous dose of aminophylline (6 mg/ kg) before and after the oral administration of fluconazole 200 mg daily for 14 days in 16 normal male volunteers. There were significant increases in theophylline AUC, Cmax, and half-life with a corresponding decrease in clearance. The mean ± SD theophylline AUC increased 21% ± 16% (range: ?5 to 48%). The Cmax increased 13% ± 17% (range: ?13 to 40%). Theophylline clearance decreased 16% ± 11% (range: ?32 to 5%). The half-life of theophylline increased from 6.6 ± 1.7 hours to 7.9 ± 1.5 hours. (See PRECAUTIONS.)

Terfenadine

Six healthy volunteers received terfenadine 60 mg BID for 15 days. Fluconazole 200 mg was administered daily from days 9 through 15. Fluconazole did not affect terfenadine plasma concentrations. Terfenadine acid metabolite AUC increased 36% ± 36% (range: 7 to 102%) from day 8 to day 15 with the concomitant administration of fluconazole. There was no change in cardiac repolarization as measured by Holter QTc intervals. Another study at a 400-mg and 800-mg daily dose of fluconazole demonstrated that DIFLUCAN taken in doses of 400 mg per day or greater significantly increases plasma levels of terfenadine when taken concomitantly. (See CONTRAINDICATIONS and PRECAUTIONS.)
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