[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.
Cheymol
G
G
Service de Pharmacologie, Hôpital St Antoine, Paris.
Poirier
J M
JM
D000935:Antifungal Agents / Q000097:blood / Q000627:therapeutic use*; D001228:Aspergillosis / Q000097:blood / Q000188:drug therapy*; D016022:Case-Control Studies; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D017964:Itraconazole / Q000097:blood / Q000627:therapeutic use*; D009503:Neutropenia / Q000382:microbiology*
D000935:Antifungal Agents; D017964:Itraconazole
Prophylaxie de l'aspergillose par l'itraconazole chez les patients neutropéniques: valeur des dosages plasmatiques.