CYP2C9 has a polymorphic distribution in the population and is missing in 1% of Caucasians. It is the major enzyme responsible for metabolism of many of the non-steroidal anti-inflammatory drugs (NSAIDs), including the second generation cyclooxygenase-2 (COX-2) specific inhibitors. A number of other important medications have their metabolism primarily catalyzed by CYP2C9. An important drug metabolized by this enzyme is warfarin (Coumadin ), and almost all inter-patient variability in warfarin levels and anticoagulant effects can be explained on the basis of CYP2C9 activity (not the differences in protein binding as originally thought). Most of the traditional NSAIDs and the COX-2 specific drugs are metabolized by CYP2C9.
The azole antifungal agent fluconazole(Diflucan) is a potent inhibitor of CYP2C9. Fluconazole, at conventional doses, abolishes CYP2C9 activity. An interaction between fluconazole and warfarin results in at least a 2-fold increase in warfarin blood level, a reduction in warfarin clearance, and increased anticoagulation.{Black} Clinical studies have identified a significant interaction between fluconazole and celecoxib (Celebrex), leading to a 2-fold increase in celecoxib plasma concentrations.{Celebrex} A clinical pharmacokinetic study showed an increase in phenytoin area under the plasma concentration curve (AUC) following fluconazole administration,{Touchette et al 1992} and symptomatic phenytoin toxicity has been reported with concomitant administration of fluconazole and phenytoin.{Cadle et al 1994}

Celebrex. Physicians' Desk Reference. Montvale, NJ: Medical Economics Company, Inc., 2001: 2482-2485.
Black DJ, Kunze KL, Wienkers LC, Gidal BE, Seaton TL, McDonnell ND et al. Warfarin-fluconazole. II. A metabolically based drug interaction: in vivo studies. Drug Metab Dispos 1996; 24(4):422-428.
Cadle RM, Zenon GJ, III, Rodriguez-Barradas MC, Hamill RJ. Fluconazole-induced symptomatic phenytoin toxicity. Ann Pharmacother 1994; 28(2):191-195.
Touchette MA, Chandrasekar PH, Milad MA, Edwards DJ. Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man. Br J Clin Pharmacol 1992; 34(1):75-78.