title: A retrospective analysis of the effect of patient-specific factors on voriconazole concentrations in oncology patients.
abstract: OBJECTIVE
  To identify patient-specific factors significantly associated with voriconazole exposure. DESIGN SETTING, AND PARTICIPANTS: Retrospective, single center at an academic medical center. Consecutive, adult oncology inpatients who received voriconazole by mouth and had at least one voriconazole level over a 14-month period. Voriconazole was ordered for 292 patients during the study period, a level was obtained in 41 patients. Nine patients were excluded; the study population was comprised of 32 patients.
  
  
  RESULTS
  Univariate and multivariable regression analyses were utilized to predict the patient-specific factors significantly associated with level. A total of 36 levels meeting inclusion/exclusion criteria were performed in 32 patients. Sixty percent of levels (22/36) were between 1 and 5.5 µg/mL. Data were available to calculate a Child Pugh score for 66% (21/32) of patients. Using multivariable linear regression, three covariates were found to be statistically significant: age, international normalized ratio (INR), and alkaline phosphatase (ALP). Three outliers were notable in the ALP category, when removing the three individuals from the model, only an increasing INR remains significantly associated with increasing voriconazole level (p = 0.0093). No correlation was found with trough level and Child Pugh score.
  
  
  CONCLUSIONS
  Sixty percent of voriconazole trough levels were between 1 and 5.5 µg/mL (range 0.1-7.4 µg/mL), only increasing INR was significantly associated with rising voriconazole level. Increasing Child Pugh score was not associated with increasing level. More investigation is warranted into the usefulness of the Child Pugh score for guidance of dose modifications in non-cirrhotic patients with acute hepatic injury.
authors.affiliation: Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD, USA. llombar3@jhmi.edu
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Lombardi
authors.forename: Todd A
authors.initials: TA
authors.lastname: Miano
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Davis
authors.forename: Steven C
authors.initials: SC
authors.lastname: Morgan
authors.forename: Steven C
authors.initials: SC
authors.lastname: Goldstein
authors.forename: Saran
authors.initials: S
authors.lastname: Vardhanabhuti
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
authors.forename: J Michael
authors.initials: JM
authors.lastname: Vozniak
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009181:Mycoses / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D009369:Neoplasms / Q000150:complications*; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012189:Retrospective Studies; D014230:Triazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000469:Alkaline Phosphatase; D065819:Voriconazole