PHARMACOKINETICS OF ITRACONAZOLE

Itraconazole is a lipophilic triazole antifungal with a broad spectrum of activity. Most of the important fungal pathogens respond to itraco nazole concentrations of 100 ng/ml. Therefore, itraconazole is suitabl e for treatment of a variety of systemic mycoses, as aspergillosis, cr yptococcosis, candidosis as well as non-European endemic mycoses. The lipophilicity of the molecule is the reason for a pronounced tissue af finity meaning that the tissue levels of the drug usually are substant ially higher than the corresponding plasma levels. This fact has to be kept in mind when plasma measurements are being used to decide a ther apeutic approach for a systemic fungal infection. In contrast to the s kin, internal organs will not show a long term retention of itraconazo le in the tissues. This means that for systemic mycoses the therapy ne eds to be continued until clinical and mycological cure is obtained. R educed itraconazole absorption may occur in a minority of patients bec ause of underlying chemotherapy or dramatic changes in stomach pH. Thi s is occasionally seen in patients with allogeneic bone marrow transpl ants and end-stage AIDS patients. Use of antacida and H-2-antagonists somewhat reduces the absorption of itraconazole, however, often not in a clinically meaningful way. Itraconazole increases the levels of cyc losporin A. Itraconazole levels are decreased by rifampicin, phenytoin and phenobarbital. Caution is required in patients on concomitant ant icoagulants.