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Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole

Brad Moriyama1, Sameer Kadri2, Stacey A Henning1

  • 1NIH Clinical Center, Pharmacy Department, Bethesda, MD.

Current Fungal Infection Reports
|February 27, 2016
PubMed

Insights

Voriconazole therapeutic drug monitoring (TDM) shows benefits for patients, but more high-quality trials are needed. CYP2C19 genotyping alone is insufficient for guiding voriconazole dosing due to variability in clinical settings.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Genetics

Background:

  • Voriconazole is a crucial antifungal for invasive aspergillosis.
  • Its metabolism involves CYP2C19, CYP2C9, and CYP3A4, leading to significant interpatient variability in serum concentrations.
  • CYP2C19 genetic polymorphisms are implicated in this pharmacokinetic variability.

Purpose of the Study:

  • To review evidence on voriconazole therapeutic drug monitoring (TDM).
  • To assess the role of CYP2C19 genotyping in optimizing voriconazole dosing strategies.
  • To identify gaps in current research for clinical implementation.

Main Methods:

  • Systematic review of studies evaluating voriconazole TDM efficacy and safety.
  • Analysis of the relationship between CYP2C19 genotype and voriconazole pharmacokinetics in healthy volunteers and patients.
  • Examination of the practical challenges of integrating genotyping into clinical practice.

Main Results:

  • Most observational studies suggest TDM is beneficial for voriconazole therapy.
  • A strong link between CYP2C19 genotype and voriconazole pharmacokinetics exists in healthy individuals, but is less pronounced in patients.
  • Current evidence, primarily from observational studies, is insufficient for definitive TDM guidelines.

Conclusions:

  • Voriconazole TDM appears beneficial, but robust randomized controlled trials are lacking.
  • CYP2C19 genotyping alone cannot reliably guide initial voriconazole dosing in clinical practice.
  • Further research is required before routine implementation of CYP2C19 genotyping for voriconazole dosing.
Keywords:
CYP2C19pharmacogenomicspharmacokineticsvoriconazole

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