Pharmacogenetics and beyond: variability of voriconazole plasma levels in a patient with primary immunodeficiency

Pharmacogenomics. 2012 Dec;13(16):1961-5. doi: 10.2217/pgs.12.175.

Abstract

We report the case of a patient highly susceptible to invasive aspergillosis who received treatment with voriconazole (VRC). As part of therapeutic drug monitoring, VRC plasma trough concentrations were measured, showing undetectable levels (<0.16 µg/ml). Genotyping showed a heterozygous profile CYP2C19*1/*17, known to be associated with an ultrarapid-metabolism phenotype, contributing to the very low systemic exposure observed. Therefore, in this situation, the use of VRC treatment could be associated with therapeutic failure.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aspergillosis* / chemically induced
  • Aspergillosis* / drug therapy
  • Aspergillosis* / genetics
  • Aspergillosis* / pathology
  • Cytochrome P-450 CYP2C19
  • Genetic Association Studies
  • Granulomatous Disease, Chronic* / drug therapy
  • Granulomatous Disease, Chronic* / genetics
  • Humans
  • Male
  • Pharmacogenetics
  • Pyrimidines* / administration & dosage
  • Pyrimidines* / adverse effects
  • Pyrimidines* / blood
  • Triazoles* / administration & dosage
  • Triazoles* / adverse effects
  • Triazoles* / blood
  • Voriconazole

Substances

  • Pyrimidines
  • Triazoles
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Voriconazole