The synthetic triazoles include:
Fluconazole belongs to a class of synthetic, broad-spectrumtriazoles and is also referred to as a bistriazole antimycotic drug.
Itraconazole and voriconazole also belong to the synthetic tri-azole class of drugs. They inhibit the synthesis of ergosterol, a vi-tal component of fungal cell membranes.
After oral administration, fluconazole is about 90% absorbed. It’s distributed into all body fluids, and more than 80% of the drug is excreted unchanged in urine.
Oral bioavailability is greatest when itraconazole is taken with food; voriconazole is more effective if taken 1 hour before or after a meal.
Itraconazole and voriconazole are bound to plasma proteins and extensively metabolized in the liver into a large number of metabolites. They’re minimally excreted in stool.
Fluconazole inhibits fungal cytochrome P-450, an enzyme respon-sible for fungal sterol synthesis, causing fungal cell walls to weak-en.
Itraconazole and voriconazole interfere with fungal cell-wall synthesis by inhibiting the formation of ergosterol and increasing cell-wall permeability, making the fungus susceptible to osmotic instability.
Fluconazole is used to treat mouth, throat, and esophageal can-didiasis and serious systemic candidal infections, including UTIs, peritonitis, and pneumonia. It’s also used to treat cryptococcal meningitis.
Itraconazole is used to treat blastomycosis, nonmeningeal histo-plasmosis, candidiasis, aspergillosis, and fungal nail disease. Voriconazole is used to treat invasive aspergillosis and serious fungal infections caused by Scedosporium apiospermum and Fusarium species.
Fluconazole may have interactions with other drugs:
§ Using fluconazole with warfarin may increase the risk of bleed-ing.
§ It may increase levels of phenytoin and cyclosporine.
§ It may increase the plasma levels of oral antidiabetic drugs, such as glyburide, tolbutamide, and glipizide, increasing the risk of hypoglycemia.
§ Rifampin and cimetidine enhance the metabolism of flucona-zole, reducing its plasma level.
§ Fluconazole may increase the activity of zidovudine. (See Ad-verse reactions to synthetic triazoles.)
Itraconazole and voriconazole may have these interactions:
§ Both may increase the risk of bleeding when combined with oral anticoagulants.
§ Antacids, H2-receptor antagonists, phenytoin, and rifampin low-er plasma itraconazole levels.
§ Voriconazole may inhibit the metabolism of phenytoin, benzodi-azepines, calcium channel blockers, sulfonylureas, and tacrolimus.
§ Voriconazole is contraindicated with sirolimus and ergot alka-loids because voriconazole may increase plasma levels of sirolimus and ergots.
§ Voriconazole is contraindicated with quinidine and pimozide be-cause of the risk of prolonged QT interval and, rarely, torsades de pointes.