Effect of antifungal drugs on cytochrome P450 (CYP) 1A2, CYP2D6, and CYP2E1 activities in human liver microsomes.
Article Details
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Niwa T, Inoue-Yamamoto S, Shiraga T, Takagi A
Effect of antifungal drugs on cytochrome P450 (CYP) 1A2, CYP2D6, and CYP2E1 activities in human liver microsomes.
Biol Pharm Bull. 2005 Sep;28(9):1813-6.
- PubMed ID
- 16141569 [ View in PubMed]
- Abstract
The effects of five antifungal drugs, fluconazole, itraconazole, micafungin, miconazole, and voriconazole, on cytochrome P450 (CYP) 1A2-mediated 7-ethoxyresorufin O-deethylation, CYP2D6-mediated debrisoquine 4-hydroxylation, and CYP2E1-mediated chlorzoxazone 6-hydroxylation activities in human liver microsomes were compared. In addition, the effect of preincubation was estimated in order to investigate the mechanism-based inhibition. IC50 values of miconazole against CYP1A2 and CYP2D6 activities were 2.90 and 6.46 microM, respectively, and miconazole at 10 microM concentration slightly inhibited CYP2E1 activity. On the other hand, other antifungal drugs neither inhibited nor stimulated all of the metabolic activities. The stimulation of the inhibition of the metabolic activities mediated by CYP1A2, CYP2D6, or CYP2E1 by 15-min preincubation was not observed for any of the antifungal drugs, suggesting that these antifungal drugs are not mechanism-based inhibitors. These results suggest that miconazole is the strongest inhibitor against CYP1A2, CYP2D6, and CYP2E1 among the antifungal drugs investigated.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Miconazole Cytochrome P450 2D6 Protein Humans UnknownInhibitorDetails Miconazole Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareVenlafaxineVoriconazole The risk or severity of adverse effects can be increased when Voriconazole is combined with Venlafaxine.