Itraconazole decreases ergosterol biosynthesis by interfering with cytochrome P450 activity. This inhibits cell membrane function of susceptible fungi including Microsporum species, Trichophyton species, Candida species, Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatitidis and Paracoccidiodes brasiliensis. It also has antiprotozoal activity against Leishmania major.

Absorption
Absorbed from the GIT, capsule enhanced by acidic gastric environment or when taken with food; oral liquid better absorbed during fasting state. Peak plasma concentrations are achieved after 1.5-5 hours.

Distribution
Itraconazole is extensively bound (99.8%) to plasma protein. Widely distributed in skin, sebum, pus and other tissues and organs (higher concentrations compared to plasma). Small amounts are distributed in CSF and breast milk.

Metabolism
Undergoes saturable hepatic metabolism (via cytochrome P450 isoenzyme CYP3A4); converted to hydroxyitraconazole (antifungal activity comparable to the parent drug) and other metabolites.

Excretion
Via urine or bile (as inactive metabolites), via faeces (3-18% as unchanged), stratum corneum and hair (small amounts); not removed by dialysis.

Dyspepsia, abdominal pain, nausea, vomiting, diarrhoea; menstrual disorders; constipation, rash, pruritus, urticaria; angioedema, anaphylaxis. Increased liver enzyme values, jaundice, Stevens-Johnson syndrome, hypokalaemia.