The Azoles Antifungal Drug

THE AZOLES

Azole antifungal drugs are synthetic compounds with broad-spectrum fungistatic activity. Azoles can be di-vided into two groups: the older imidazole agents, in which the five-member azole nucleus contains two ni-trogens, and the newer triazole compounds, fluconazole and itraconazole, in which the azole nucleus contains three nitrogens.

All azoles exert antifungal activity by binding to cy-tochrome P450 enzymes responsible for the demethyla-tion of lanosterol to ergosterol. Reduced fungal mem-brane ergosterol concentrations result in damaged, leaky cell membranes. The toxicity of these drugs de-pends on their relative affinities for mammalian and fungal cytochrome P450 enzymes. The triazoles tend to have fewer side effects, better absorption, better drug distribution in body tissues, and fewer drug interactions.