Drug interaction between oral solution itraconazole and calcineurin inhibitors in allogeneic hematopoietic stem cell transplantation recipients: an association with bioavailability of oral solution itraconazole

Int J Hematol. 2009 Jul;90(1):103-107. doi: 10.1007/s12185-009-0344-z. Epub 2009 May 27.

Abstract

To assess the drug interaction between oral solution itraconazole and calcineurin inhibitors, 10 recipients of allogeneic hematopoietic stem cell transplantation (HSCT), in whom oral solution itraconazole was started when they had been on a steady dose of calcineurin inhibitors (cyclosporine A or tacrolimus), were retrospectively evaluated. The concentration/dose [C/D; (ng/mL)/(mg/kg)] ratio of calcineurin inhibitors significantly increased after initiating oral solution itraconazole, and the increase at 7-10 days after initiating itraconazole was 93.7%, ranging from 37.3 to 328.2%. The plasma level of itraconazole/hydroxyitraconazole was significantly correlated with the increase in the C/D ratio of calcineurin inhibitors (correlation coefficient, 0.65; P < 0.05). These results suggest that oral solution itraconazole significantly interacts with calcineurin inhibitors with a wide interindividual variability in allogeneic HSCT recipients, which could partly be explained by the variable bioavailability of oral solution itraconazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacokinetics
  • Calcineurin / pharmacokinetics
  • Calcineurin Inhibitors*
  • Cyclosporine / administration & dosage*
  • Cyclosporine / pharmacokinetics
  • Drug Interactions
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / pharmacokinetics
  • Itraconazole / administration & dosage*
  • Itraconazole / pharmacokinetics
  • Male
  • Retrospective Studies
  • Tacrolimus / administration & dosage*
  • Tacrolimus / pharmacokinetics
  • Transplantation, Homologous

Substances

  • Antifungal Agents
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Itraconazole
  • Cyclosporine
  • Calcineurin
  • Tacrolimus