[Prevention of aspergillosis with itraconazole in neutropenic patients: importance of drug monitoring].

Itraconazole is being used increasingly as prophylaxis of systemic aspergillosis in patients with immunodepression. Therapeutic itraconazole monitoring by plasma concentrations measurement is justified by its dose-dependent pharmacokinetics, drug interactions, and frequent bioavailability modifications observed in immunocompromised patients. A first study was carried out in 16 patients with haematological malignancies, given chemotherapy plus itraconazole 400-800 mg/day in a single dose as prophylactic treatment. Therapeutic through drug plasma concentration (Cmin > or = 250 ng/ml of itraconazole, or > or = 750 ng/ml of itraconazole plus hydroxyitraconazole) was not reached in 5/16 patients. Moreover results emphasised the wide inter and intra-individual variability of the steady-state plasma concentrations. In another study we used a multiple dose regimen (100-200 mg x 3/day), instead of a single dose regimen. An adequate Cmin value was found in 34/36 patients. In conclusion, the wide inter and intra-individual variability of itraconazole pharmacokinetics necessitate regularly to measure the drug plasma concentrations in patients with life-threatening fungal infections.