title: Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities.
abstract: This study investigated the relationship between plasma voriconazole concentrations (pVC) and risk of visual adverse events (VAEs) or liver function test (LFT) abnormalities using longitudinal logistic regression. Seven-day mean pVC were calculated from 2,925 plasma samples (1,053 patients); in each 7-day period, the presence or absence of VAEs/abnormal LFTs was analyzed as a binary outcome variable. There was a relationship between pVC and risk of VAE (P = .011) and a weaker, but statistically significant, association with risk of aspartate transaminase (AST), alkaline phosphatase (ALP), or bilirubin but not alanine transaminase (ALT) abnormalities. The odds ratios of LFT abnormalities per 1 mug/mL pVC increase ranged from 1.07 to 1.17. Maximum weekly occurrences were 10%, 8%, 5%, and 14% for AST, ALT, ALP, and bilirubin abnormalities, respectively. Receiver-operating characteristic curve analysis indicates that individual pVC cannot be used to predict subsequent LFT abnormalities.
authors.affiliation: Clinical R&D, IPC 096, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, CT13 9NJ, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Tan
authors.forename: Nigel
authors.initials: N
authors.lastname: Brayshaw
authors.forename: Konrad
authors.initials: K
authors.lastname: Tomaszewski
authors.forename: Peter
authors.initials: P
authors.lastname: Troke
authors.forename: Nolan
authors.initials: N
authors.lastname: Wood
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000935:Antifungal Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D011743:Pyrimidines / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D012372:ROC Curve; D012044:Regression Analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D014230:Triazoles / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D014786:Vision Disorders / Q000139:chemically induced*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D065819:Voriconazole