title: Serum voriconazole level variability in patients with hematological malignancies receiving voriconazole therapy.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Hematology, Department of Medicine, University of Alberta, Edmonton, Alberta;
authors.forename: Lalit
authors.initials: L
authors.lastname: Saini
authors.affiliation: Department of Pharmacy, Princess Margaret Cancer Centre; ; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario;
authors.forename: Jack T
authors.initials: JT
authors.lastname: Seki
authors.affiliation: Transplant Infectious Diseases, Alberta Transplant Institute; ; University of Alberta, Edmonton, Alberta;
authors.forename: Deepali
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Biostatistics Department, Princess Margaret Cancer Centre;
authors.forename: Eshetu G
authors.initials: EG
authors.lastname: Atenafu
authors.affiliation: Department of Laboratory Medicine and Pathophysiology and Department of Clinical Pathology, University of Toronto; ; Department of Clinical Pathology, Sunnybrook Health Sciences Centre;
authors.forename: David Ec
authors.initials: DE
authors.lastname: Cole
authors.affiliation: Department of Clinical Pathology, Sunnybrook Health Sciences Centre;
authors.forename: Betty Yl
authors.initials: BY
authors.lastname: Wong
authors.affiliation: Laboratory Medicine Program, Toronto General Hospital, University Health Network; ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario.
authors.forename: Andrea
authors.initials: A
authors.lastname: Božović
authors.affiliation: Division of Hematology, Department of Medicine, University of Alberta, Edmonton, Alberta;
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Brandwein
keywords: Antifungals; Drug levels; Liver toxicity; Voriconazole