Drug interactions with fluconazole.
Fluconazole, a water-soluble bis-triazole antifungal agent that effectively penetrates the cerebrospinal fluid, is a highly selective inhibitor of the fungal cytochrome P450 system. In single-dose studies, coadministration of cimetidine and fluconazole (100 mg) resulted in an insignificant decrease in the absorption of fluconazole. The coadministration of rifampin and fluconazole (200 mg) decreased both the half-life and the area under the plasma concentration-time curve (AUC) of fluconazole. In multiple-dose studies, fluconazole (50 mg) did not significantly alter the pharmacokinetics of the two steroid components of an oral contraceptive. Coadministration of tolbutamide with fluconazole (100 mg) increased both the maximal plasma concentration and the AUC of tolbutamide without changing levels of blood glucose. The coadministration of cyclosporin A with a low dose of fluconazole (100 mg) was not associated with significant changes in the minimal and the maximal plasma concentrations of cyclosporin A. While higher doses of fluconazole (200 mg) did not affect endogenous steroids, coadministration resulted in changes in the pharmacodynamics of warfarin and the pharmacokinetics of phenytoin and cyclosporin A.
Lazar
J D
JD
Department of Clinical Research, Pfizer Central Research, Groton, Connecticut 06340.
Wilner
K D
KD
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000983:Antipyrine / Q000493:pharmacokinetics; D002927:Cimetidine / Q000493:pharmacokinetics; D003278:Contraceptives, Oral, Hormonal / Q000493:pharmacokinetics; D003524:Cyclosporins / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000493:pharmacokinetics; D012293:Rifampin / Q000494:pharmacology; D013739:Testosterone / Q000378:metabolism; D014044:Tolbutamide / Q000493:pharmacokinetics; D014859:Warfarin / Q000494:pharmacology
D003278:Contraceptives, Oral, Hormonal; D003524:Cyclosporins; D013739:Testosterone; D014859:Warfarin; D010672:Phenytoin; D002927:Cimetidine; D015725:Fluconazole; D014044:Tolbutamide; D000983:Antipyrine; D012293:Rifampin