Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-β-cyclodextrin oral solution or coated-pellet capsules

We have previously shown that a trough concentration of at least 500 ng ml(-1) itraconazole is necessary for an effective antifungal prophylaxis in neutropenic patients. Since the bioavailability of itraconazole is reduced in these patients, a satisfactory dosing regimen remains to be defined. In this study, six dosing regimens with itraconazole capsules 400, 600 or 800 mg day(-1) itraconazole solution 400 mg day(-1) (additional loading dose: 400 mg day(-1) solution for 2 days), 800 mg day(-1) or 400 mg day(-1) (additional loading dose: 800 mg day(-1) capsules for 7 days, s/c1200) were compared during 160 courses of myelosuppressive chemotherapy in 123 patients with acute leukaemia. After the first week, patients taking 800 mg day(-1) or 400 mg day(-1) (s/c1200) itraconazole solution achieved significantly higher trough concentrations (high-performance liquid chromatography) than patients in other groups (P < 0.05) and 87 and 100%, respectively, of these had concentrations > 500 ng ml(-1). Contrary to a dose of 400 mg day(-1), a dose of 800 mg day(-1) itraconazole solution induced severe nausea and vomiting in 46% of the patients. We conclude that 400 mg day(-1) itraconazole solution with a loading dose of 800 mg day(-1) capsules for 7 days resulted in sufficient trough concentrations from the first week onwards and appears to be suitable for antifungal prophylaxis in neutropenic patients.