The synthetic triazoles include:
Fluconazole belongs to a class of synthetic, broad-spectrumtriazoles and is also
referred to as a bistriazole antimycotic
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
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
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
§ 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
Itraconazole and voriconazole may have these
§ Both may increase the risk of bleeding when
combined with oral anticoagulants.
§ Antacids, H2-receptor antagonists, phenytoin, and rifampin low-er plasma
§ Voriconazole may inhibit the metabolism of
phenytoin, benzodi-azepines, calcium channel blockers, sulfonylureas, and
§ 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.