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Canadian Journal of Infectious Diseases and Medical Microbiology
Volume 25, Issue 5, Pages 271-276
Original Article

Serum Voriconazole Level Variability in Patients with Hematological Malignancies Receiving Voriconazole Therapy

Lalit Saini,1 Jack T Seki,2,3 Deepali Kumar,4,5 Eshetu G Atenafu,6 David EC Cole,7,8 Betty YL Wong,8 Andrea Božović,9,10 and Joseph M Brandwein1

1Division of Hematology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
2Department of Pharmacy, Princess Margaret Cancer Centre, Canada
3Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
4Transplant Infectious Diseases, Alberta Transplant Institute, Canada
5University of Alberta, Edmonton, Alberta Transplant Institute, Canada
6Biostatistics Department, Princess Margaret Cancer Centre, Canada
7Department of Laboratory Medicine and Pathophysiology and Department of Clinical Pathology, University of Toronto, Canada
8Department of Clinical Pathology, Sunnybrook Health Sciences Centre, Canada
9Laboratory Medicine Program, Toronto General Hospital, University Health Network, Canada
10Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

Copyright © 2014 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


INTRODUCTION: Voriconazole plasma concentrations have been correlated with oral dosing in healthy subjects, but have been poorly characterized in ill patients with hematological malignancies receiving intensive chemotherapy.

METHODS: The relationship between orally administered voriconazole, plasma concentrations and liver toxicity was examined in a cohort of 69 primarily acute leukemia patients undergoing intensive chemotherapy.

RESULTS: Oral administration of voriconazole was associated with significant interpatient variability, with voriconazole steady-state concentrations ranging from 0 μg/mL to 16.6 μg/mL. Approximately 20% of patients achieved steady-state concentrations <1 μg/mL. When adjusted for weight, patients receiving higher voriconazole doses tended toward higher plasma concentrations; however, there was no significant relationship between the plasma concentration and genotype, age, sex or use of concomitant proton pump inhibitors. Voriconazole concentrations were correlated with higher serum alkaline phosphatase levels at day 6 to 8, and with higher bilirubin and aspartate aminotransferase levels at day 14 to 16, but not with other liver enzyme levels.

CONCLUSION: In ill patients with acute leukemia and related disorders undergoing treatment with oral voriconazole, there is a poor correlation between the voriconazole dose and plasma concentrations, and many patients achieve levels that are considered to be subtherapeutic. The findings support the routine use of therapeutic drug monitoring in these patients.