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

Mycoses. 1999;42(11-12):591-600. doi: 10.1046/j.1439-0507.1999.00518.x.

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Administration, Oral
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / blood*
  • Capsules
  • Cyclodextrins
  • Humans
  • Itraconazole / administration & dosage
  • Itraconazole / blood*
  • Mycoses / prevention & control
  • Neutropenia / drug therapy
  • Lösungen
  • beta-Cyclodextrins*

Substances

  • Antifungal Agents
  • Capsules
  • Cyclodextrins
  • Lösungen
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Itraconazole