Klin Farmakol Farm. 2009;23(2):86-89

Azole antimycotics: Mechanisms of drug-drug interactions

Lucie Krausová¹, Jiří Grim², Petr Pávek¹

¹ Katedra farmakologie a toxikologie, Farmaceutická fakulta v Hradci Králové, Univerzita Karlova v Praze

² Interní klinika, Fakultní nemocnice, Hradec Králové

Altough the therapy of fungal infections has been developing for many years, searching of optimal drugs and pharmacotherapeutic approach

is still desirable due to the increasing prevalence of systemic mycoses with high risk of mortality. In comparison with the past, currently we

dispose of more efficacious drugs with lower adverse effects. Significant progress has been done in terms of reduction of adverse effects

of azole antifungals and heightening of their specificity for pathogen. Nevertheless drug-drug interactions, which may occur in 95 % in

patients treated with combination of azole antimycotics and other drugs, still complicate the pharmacotherapy of systemic mycoses.

The most important and best known mechanism of drug-drug interactions caused by azole antimycotics is the inhibition of metabolizing

enzymes of cytochrome P450 (CYP) family. Moreover during several years additional mechanisms of pharmacokinetic drug-drug

interactions have been studied and described for the drugs such as inhibition of membrane transport protein, namely P-glycoprotein

(P-gp), and regulation of expression of metabolizing enzymes, especially CYP3A4 via pregnane X receptor (PXR).

In present review we focus on the last two mentioned mechanisms of drug-drug interactions caused by azole antimycotics, affecting the

transport functions of P-gp and modulation of expression of enzymes involved in I. and II. phases of biotransformation.

Keywords: drug-drug interactions, azole antimycotics, systemic mycoses, P-glycoprotein, PXR, CYP3A4.

Published: July 1, 2009  Show citation