Itraconazole: pharmacokinetics and indications

Abstract

Itraconazole is a highly lipophilic triazolic compound, scarcely soluble in acidified polyethylene glycol, and soluble in hydroxypropyl-beta-cyclodextrin. It possesses an excellent digestive adsorption and its peak plasma level after oral administration of 100 mg is 0.16 microgram/ml at 3 or 4 h after drug intake. Half-life of itraconazole ranges between 17 to 21 h and 99.8% binds to plasmatic proteins, especially albumin. Metabolization is mainly done in the liver where inactive metabolites are formed with the exception of hydroxy-itraconazole, which exhibits a discrete antifungal activity. Stabilization of blood levels with repeated drug administration is reached at day 14, showing an increase both in plasma concentrations and in its half-life. Tissue levels of itraconazole are 3- to 20-fold higher than plasmatic concentrations, whereas only negligible concentrations are in CSF and urine. In the skin and particularly nails, itraconazole persists for a long time after discontinuation of therapy. Its mechanism of action is similar to other azolic compounds, inhibiting the alpha-14-demethylase of lanosterol which interferes with the synthesis of ergosterol. This drug behaves as a wide spectrum antifungal agent, acting against most pathogenic fungi with the exception of the Zygomycetes. Daily doses vary, according to indications, from 100 to 400 mg. The efficacy and results obtained in dermatomycosis, candidiasis, paracoccidioidomycosis, keratomycosis, sporotrichosis, chromoblastomycosis, coccidioidomycosis, blastomycosis, cryptococcosis, phaeohyphomycosis and maduromycotic mycetomas are detailed.