The Enzymatic Basis of Drug-Drug Interactions with Systemic Triazole Antifungals
Fiche publication
Date publication
janvier 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HERBRECHT Raoul, Pr UBEAUD-SEQUIER Genevieve
Tous les auteurs :
Nivoix Y, Leveque D, Herbrecht R, Koffel JC, Beretz L, Ubeaud-Sequier G
Lien Pubmed
Résumé
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.
Référence
Clin Pharmacokinet. 2008;47(12):779-92