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.