ATCvet code: QJ02AC02
Pharmacodynamic properties
The mode of action of itraconazole is based on its highly selective binding ability to fungal Cytochrome P-450 iso-enzymes. This inhibits the synthesis of ergosterol and affects membrane-bound enzyme function and membrane permeability. This effect is irreversible and causes structural degeneration.
Pharmacokinetic particulars
Laboratory animals rapidly absorb orally administered itraconazole. It binds very extensively to plasma proteins (>99 %) and distributes to tissues. More than 30 metabolites are formed, from which hydroxy-itraconazole has an antifungal activity as the parent. Excretion is rapid and mainly via the faeces.
In cats a single oral dose of 5 mg/kg results in maximum plasma concentrations of on average 0.525 mg/l attained 2 hours after dosing. The AUC0-24 h is 5 mg.h/l. The half-life in plasma is about 12 hours. After repeated administration for one week at 5 mg/kg/day, the maximum plasma concentration is more than doubled. The AUC0-24 h is increased 3 times to 15 mg.h/l and the plasma half-life is also increased 3 times to 36 hours.
In the therapeutic treatment schedule, itraconazole is almost completely cleared from plasma after each wash-out. In contrast to what happens in other animals, hydroxyitraconazole remains near or below the quantification limit in plasma after a single dose of itraconazole at 5 mg/kg. Concentrations in cat’s hair vary; an increase occurs during treatment to a median value of 3.0 μg/g (mean 5.2 μg/g) at the end of the third dosing week and concentrations drop slowly to 1.5 μg/g (mean 1.9 μg/g) at 14 days after the end of treatment. Concentrations of hydroxy-itraconazole in hair are insignificant.
Bioavailability of the oral solution of itraconazole in humans is higher when administered in fasted conditions.