Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities

J Clin Pharmacol. 2006 Feb;46(2):235-43. doi: 10.1177/0091270005283837.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Antifungal Agents / adverse effects*
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / blood*
  • Cohort Studies
  • Female
  • Humans
  • Liver Function Tests
  • Male
  • Pyrimidines / adverse effects*
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics
  • ROC Curve
  • Regression Analysis
  • Retrospective Studies
  • Risk Assessment
  • Triazoles / adverse effects*
  • Triazoles / blood
  • Triazoles / pharmacokinetics
  • Vision Disorders / chemically induced*
  • Voriconazole

Substances

  • Antifungal Agents
  • Pyrimidines
  • Triazoles
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Voriconazole