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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 12/2008

01-12-2008 | Review Article

The Enzymatic Basis of Drug-Drug Interactions with Systemic Triazole Antifungals

Authors: Dr Yasmine Nivoix, Dominique Levêque, Raoul Herbrecht, Jean-Claude Koffel, Laurence Beretz, Genevieve Ubeaud-Sequier

Published in: Clinical Pharmacokinetics | Issue 12/2008

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Abstract

Drug-drug interactions are a recurring problem in immunocompromised patients treated with triazole antifungals. While the introduction of new antifungals has expanded opportunities for lowering drug toxicity, virtually all antifungal regimens carry the risk of pharmacokinetic and pharmacodynamic interaction. This review presents the published data on molecular determinants (enzymes, transporters, orphan nuclear receptors) of systemic triazole pharmacokinetics in humans, including itraconazole, fluconazole, voriconazole and posaconazole. Systemic triazoles are inhibitors of cytochrome P450 (CYP) isozymes, such as CYP3A4, CYP2C9 and CYP2C19, to varying degrees. In addition, some are substrates and/or inhibitors of drug transporters such as multidrug resistance-1 gene product, P-glycoprotein, or breast cancer resistance protein. The interactions of triazole antifungals can be divided into the following categories: modifications of antifungal pharmacokinetics by other drugs, modifications of other drug pharmacokinetics by antifungals, and two-way interactions. These features are the basis of most interactions that occur during triazole therapy.
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Metadata
Title
The Enzymatic Basis of Drug-Drug Interactions with Systemic Triazole Antifungals
Authors
Dr Yasmine Nivoix
Dominique Levêque
Raoul Herbrecht
Jean-Claude Koffel
Laurence Beretz
Genevieve Ubeaud-Sequier
Publication date
01-12-2008
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 12/2008
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/0003088-200847120-00003

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