Indications
Itraconazole is prescribed for a variety of fung·h immunocompromised and non-immunocompromised individuals. It is particularly effective for fung·he oral solution of itraconazole is specifically indicated for the treatment of oropharyng·hageal candidiasis.
Pharmacodynamics
As an antifung·hibiting·he growth of fung·h. It demonstrates in vitro efficacy against a rang·histoplasma capsulatum, Histoplasma duboisii, Aspergillus flavus, Aspergillus fumigatus, and species of Trichophyton.
Absorption
Itraconazole is efficiently absorbed following·h peak plasma levels typically achieved within two to five hours when administered as oral capsules. The oral bioavailability stands at approximately 55%. Notably, itraconazole's exposure is reduced when using·he capsule formulation compared to the oral solution at equivalent dosages. Optimal absorption necessitates sufficient gastric acidity. The drug follows non-linear pharmacokinetics, accumulating·h steady-state concentrations generally reached in about 15 days.
Metabolism
Itraconazole undergoes extensive hepatic metabolism, predominantly facilitated by the enzyme CYP3A4. The drug is broken down into over 30 metabolites, with hydroxyitraconazole being·he primary one. This metabolite exhibits antifung·hose of the parent compound. Additional metabolites of itraconazole include keto-itraconazole and N-dealkyl-itraconazole.
Mechanism of Action
Itraconazole exerts its antifungal effects by targeting and inhibiting 14α-demethylase, a key fungal cytochrome P450 enzyme responsible for converting lanosterol into ergosterol, an essential component of fungal cell membranes. Through its chemical structure, itraconazole's azole nitrogen atoms bind to the active site, specifically the haem iron, of the fungal enzyme, thereby hindering its functionality. This inhibition causes an accumulation of lanosterol and 14-methylated sterols, which increases the permeability of the fungal cell membrane, alters enzyme activities that are membrane-bound, and disrupts the synthesis of chitin. Furthermore, itraconazole has been suggested to inhibit fungal cytochrome c oxidative and peroxidative enzymes, contributing further to the compromise of fungal cell membrane integrity.
