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Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl‐β‐cyclodextrin oral solution or coated‐pellet capsules
Author(s) -
Glasmacher A.,
Hahn C.,
Molitor E.,
Marklein G.,
Sauerbruch T.,
SchmidtWolf I. G. H.
Publication year - 1999
Publication title -
mycoses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 69
eISSN - 1439-0507
pISSN - 0933-7407
DOI - 10.1046/j.1439-0507.1999.00518.x
Subject(s) - itraconazole , dosing , medicine , regimen , bioavailability , pharmacology , nausea , chemotherapy , trough concentration , vomiting , pharmacokinetics , gastroenterology , antifungal , dermatology
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.