[Pharmacokinetics of itraconazole]

Itraconazole is a lipophilic triazole antifungal with a broad spectrum of activity. Most of the important fungal pathogens respond to itraconazole concentrations of 100 ng/ml. Therefore, itraconazole is suitable for treatment of a variety of systemic mycoses, as aspergillosis, cryptococcosis, candidosis as well as non-European endemic mycoses. The lipophilicity of the molecule is the reason for a pronounced tissue affinity meaning that the tissue levels of the drug usually are substantially higher than the corresponding plasma levels. This fact has to be kept in mind when plasma measurements are being used to decide a therapeutic approach for a systemic fungal infection. In contrast to the skin, internal organs will not show a long term retention of itraconazole in the tissues. This means that for systemic mycoses the therapy needs to be continued until clinical and mycological cure is obtained. Reduced itraconazole absorption may occur in a minority of patients because of underlying chemotherapy or dramatic changes in stomach pH. This is occasionally seen in patients with allogeneic bone marrow transplants and end-stage AIDS patients. Use of antacida and H2-antagonists somewhat reduces the absorption of itraconazole, however, often not in a clinically meaningful way. Itraconazole increases the levels of cyclosporin A. Itraconazole levels are decreased by rifampicin, phenytoin and phenobarbital. Caution is required in patients on concomitant anticoagulants.