title: Association of sustained high plasma trough concentration of voriconazole with the incidence of hepatotoxicity.
abstract: BACKGROUND
  Therapeutic drug monitoring (TDM) of voriconazole is important to optimize efficacy and to minimize toxicity and intolerance. In this study, we evaluated the effect of sustained high plasma trough concentration of voriconazole on the incidence of hepatotoxicity in hospitalized Japanese patients.
  
  
  METHODS
  Thirty-nine patients were divided into 3 groups according to trough concentrations in two consecutive TDMs: <4 μg/ml in the first TDM (group A, n=25), >4 μg/ml in the first and <4 μg/ml in the second TDM (group B, n=8), and >4 μg/ml in both first and second TDMs (group C, n=6).
  
  
  RESULTS
  Incidences of hepatotoxicity in groups A, B and C were 16.0, 25.0 and 83.3%, and significant differences were observed between groups A and C and groups B and C. Multiple logistic regression analysis identified the classification into groups A, B and C as an independent variable of hepatotoxicity.
  
  
  CONCLUSIONS
  These results suggest that sustained high trough concentration of voriconazole may increase the risk of hepatotoxicity, and decreasing trough concentration to <4 μg/ml by dose adjustment after the initial TDM may reduce the incidence of hepatotoxicity in patients treated with voriconazole.
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita 879-5593, Japan. Electronic address: y-suzuki@oita-u.ac.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Issei
authors.initials: I
authors.lastname: Tokimatsu
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Sato
authors.forename: Kanako
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Yukie
authors.initials: Y
authors.lastname: Sato
authors.forename: Tomomi
authors.initials: T
authors.lastname: Goto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hashinaga
authors.forename: Hiroki
authors.initials: H
authors.lastname: Itoh
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Hiramatsu
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kadota
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D002648:Child; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D011743:Pyrimidines / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole
keywords: Hepatotoxicity; Pharmacokinetics; TDM; Therapeutic drug monitoring; Trough; Voriconazole