title: Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-beta-cyclodextrin oral solution or coated-pellet capsules.
abstract: 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.
authors.affiliation: Department of Internal Medicine I, Rheinische Friedrich-Wilhelms University, Bonn, Germany. glasmacher@uni-bonn.de
authors.forename: A
authors.initials: A
authors.lastname: Glasmacher
authors.forename: C
authors.initials: C
authors.lastname: Hahn
authors.forename: E
authors.initials: E
authors.lastname: Molitor
authors.forename: G
authors.initials: G
authors.lastname: Marklein
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: I G
authors.initials: IG
authors.lastname: Schmidt-Wolf
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood*; D002214:Capsules; D003505:Cyclodextrins; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000097:blood*; D009181:Mycoses / Q000517:prevention & control; D009503:Neutropenia / Q000188:drug therapy; D012996:Solutions; D047392:beta-Cyclodextrins
chemical_list: D000935:Antifungal Agents; D002214:Capsules; D003505:Cyclodextrins; D012996:Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017964:Itraconazole