Review paper
The influence of P-glycoprotein and certain cytochrome P-450 isoenzymes on antimycotic azoles

Systemic antifungal drugs are widely used to treat superficial dermatomycosis as well as invasive fungal infections. Similarly to other therapeutic agents, these compounds may also cause adverse effects and drug-drug interactions. In the majority of these processes transmembrane transporter P-glycoprotein and cytochrome P-450 isoenzymes are involved. They may be responsible for pharmacokinetic and pharmacodynamic interactions via either the influence on liberation, absorption, distribution, metabolism and excretion or on the modification of the treatment results. Co-administration of two or more drugs that may be substrates, inducers or inhibitors of P-glycoprotein and cytochrome P-450 isozymes can lead to alteration of the drug concentrations in biological fluids and – as a consequence – modification of clinical effects. Azole antifungals may act as substrates, inducers or inhibitors of cytochrome P-450 enzymes, mainly CYP3A4, as well as of P-glycoprotein, involved in absorption, distribution and elimination of these drugs. In this paper the most important interactions due to their application in humans are presented. They may affect not only the antifungal effect of azoles, but also the action of co-administered drugs.