@article {La Delfa49, author = {I La Delfa and Q M Zhu and Z Mo and T F Blaschke}, title = {Fluconazole is a potent inhibitor of antipyrine metabolism in vivo in mice.}, volume = {17}, number = {1}, pages = {49--53}, year = {1989}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Fluconazole, a bis-triazole antifungal, is distinguished from imidazole antifungals (e.g. ketoconazole) by its potency and pharmacokinetic characteristics. Imidazole-containing compounds are well documented to inhibit the hepatic cytochrome P-450-dependent enzyme system; whether this effect occurs with a bis-triazole agent is unknown. The [14C]antipyrine breath test was employed to investigate the effects of fluconazole on this enzyme system in CD-1 male mice. Control, ketoconazole (100 mg/kg), and fluconazole (1 and 10 mg/kg) were studied in single- and multiple-dose experiments. Fluconazole had potent inhibitory effects on the total (mean = -73\% +/- 2\%), demethylase (mean = -90\% +/- 2\%), and nondemethylase (mean = -60\% +/- 4\%) elimination rate constants (all p less than 0.001). The fraction of the administered radioactivity excreted as 14CO2 was decreased by 50-80\% in the fluconazole groups (p less than 0.001). These effects were seen after single- and multiple-dose studies; however, return to baseline occurred more quickly in the multiple-dose group. These effects were significantly more pronounced than those observed with equipotent doses of ketoconazole. These results provide evidence that fluconazole is a potent, partially selective, and reversible inhibitor of the cytochrome P-450-dependent enzyme system in mice. Future studies will be required to assess this property and possible interactions with drugs metabolized by this enzyme system in humans.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/17/1/49}, eprint = {https://dmd.aspetjournals.org/content/17/1/49.full.pdf}, journal = {Drug Metabolism and Disposition} }