Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes.
Article Details
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Niwa T, Shiraga T, Takagi A
Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes.
Biol Pharm Bull. 2005 Sep;28(9):1805-8.
- PubMed ID
- 16141567 [ View in PubMed]
- Abstract
The effects of five antifungal drugs, fluconazole, itraconazole, micafungin, miconazole, and voriconazole, on cytochrome P450 (CYP) 2C9-mediated tolbutamide hydroxylation, CYP2C19-mediated S-mephenytoin 4'-hydroxylation, and CYP3A4-mediated nifedipine oxidation activities in human liver microsomes were compared. In addition, the effects of preincubation were estimated to investigate the mechanism-based inhibition. The IC50 value against tolbutamide hydroxylation was the lowest for miconazole (2.0 microM), followed by voriconazole (8.4 microM) and fluconazole (30.3 microM). Similarly, the IC50 value against S-mephenytoin 4'-hydroxylation was the lowest for miconazole (0.33 microM), followed by voriconazole (8.7 microM) and fluconazole (12.3 microM). On the other hand, micafungin at a concentration of 10 or 25 microM neither inhibited nor stimulated tolbutamide hydroxylation and S-mephenytoin 4'-hydroxylation, and the IC50 values for itraconazole against these were greater than 10 microM. These results suggest that miconazole is the strongest inhibitor of CYP2C9 and CYP2C19, followed by voriconazole and fluconazole, whereas micafungin would not cause clinically significant interactions with other drugs that are metabolized by CYP2C9 or CYP2C19 via the inhibition of metabolism. The IC50 value of voriconazole against nifedipine oxidation was comparable with that of fluconazole and micafungin and higher than that of itraconazole and miconazole. The stimulation of the inhibition of CYP2C9-, CYP2C19-, or CYP3A4-mediated reactions by 15-min preincubation was not observed for any of the antifungal drugs, suggesting that these drugs are not mechanism-based inhibitors.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Fluconazole Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Fluconazole Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Fluconazole Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Itraconazole Cytochrome P450 3A4 Protein Humans NoSubstrateInhibitorDetails Miconazole Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Miconazole Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Voriconazole Cytochrome P450 2C9 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAceclofenacVoriconazole The serum concentration of Aceclofenac can be increased when it is combined with Voriconazole. AcemetacinVoriconazole The serum concentration of Acemetacin can be increased when it is combined with Voriconazole. AcetohexamideMiconazole The serum concentration of Acetohexamide can be increased when it is combined with Miconazole. AcetohexamideVoriconazole The serum concentration of Acetohexamide can be increased when it is combined with Voriconazole. Acetylsalicylic acidVoriconazole The serum concentration of Acetylsalicylic acid can be increased when it is combined with Voriconazole.