Itraconazole and hydroxyitraconazole

Itraconazole is used for the prophylaxis and treatment of invasive fungal infections (IFIs). The development of IFIs in patients being treated for haematological malignancies is associated with increased morbidity and mortality. As diagnosis of IFIs may be difficult, targeted prophylactic therapy is important in high-risk patients. Itraconazole is metabolised to hydroxyitraconazole, a pharmacologically active metabolite. Treatment failure has been associated with lower average plasma concentration of itraconazole (and hydroxyitraconazole) and thus monitoring plasma concentration may help in dose optimisation. In addition, hepatic metabolism of itraconazole shows significant inter- and intra-patient variation, and there is no clear dose-plasma concentration relationship. A pre-dose target plasma itraconazole concentration of 0.5 mg/L or more has been suggested for effective prophylaxis in patients being treated for haematological malignancies. Hydroxyitraconazole concentrations are normally higher than those of itraconazole.