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[Drug-drug interaction of antifungal drugs].
- Source :
-
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan [Yakugaku Zasshi] 2005 Oct; Vol. 125 (10), pp. 795-805. - Publication Year :
- 2005
-
Abstract
- This article reviews the in vitro metabolic and the in vivo pharmacokinetic drug-drug interactions with antifungal drugs, including fluconazole, itraconazole, micafungin, miconazole, and voriconazole. In the in vitro interaction studies, the effects of antifungal drugs on specific activities of cytochrome P450s (CYPs), including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, in human liver microsomes are compared to predict the possibility of drug interactions in vivo. Fluconazole, micafungin, and voriconazole have lower inhibitory effects on CYP3A4 activities than itraconazole and miconazole, and IC(50) and/or K(i) values against CYP2C9 and CYP2C19 activities are the lowest for miconazole, followed by voriconazole and fluconazole. In in vivo pharmacokinetic studies, it is well known that itraconazole is a potent clinically important inhibitor of the clearance of CYP3A4 substrates, and fluconazole and voriconazole are reported to increase the blood or plasma concentrations of not only midazolam and cyclosporine (CYP3A4 substrates) but also of phenytoin (CYP2C9 substrate) and/or omeprazole (CYP2C19/CYP3A4 substrate). On the other hand, no inhibition of CYP activities except for CYP3A4 activity by micafungin is observed in vitro, and the blood concentrations of cyclosporine and tacrolimus are not affected by coadministration of micafungin in vivo, suggesting that micafungin would not cause clinically significant interactions with drugs that are metabolized by CYPs via the inhibition of metabolism. Miconazole is a potent inhibitor of all CYPs investigated in vitro, although there are few detailed studies on the clinical significance of this except for CYP2C9. Therefore the differential effects of these antifungal drugs on CYP activities must be considered in the choice of antifungal drugs in patients receiving other drugs.
- Subjects :
- Antifungal Agents pharmacokinetics
Dose-Response Relationship, Drug
Drug Interactions
Echinocandins
Fluconazole pharmacokinetics
Fluconazole pharmacology
Humans
In Vitro Techniques
Itraconazole pharmacokinetics
Itraconazole pharmacology
Ketoconazole pharmacokinetics
Ketoconazole pharmacology
Lipopeptides
Lipoproteins pharmacokinetics
Lipoproteins pharmacology
Micafungin
Miconazole pharmacokinetics
Miconazole pharmacology
Microsomes, Liver enzymology
Peptides, Cyclic pharmacokinetics
Peptides, Cyclic pharmacology
Pyrimidines pharmacokinetics
Pyrimidines pharmacology
Triazoles pharmacokinetics
Triazoles pharmacology
Voriconazole
Antifungal Agents pharmacology
Cytochrome P-450 Enzyme Inhibitors
Subjects
Details
- Language :
- Japanese
- ISSN :
- 0031-6903
- Volume :
- 125
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
- Publication Type :
- Academic Journal
- Accession number :
- 16205037
- Full Text :
- https://doi.org/10.1248/yakushi.125.795