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Current Fungal Infection Reports
Published in: Current Fungal Infection Reports 2/2015

01-06-2015 | Pharmacology and Pharmacodynamics of Antifungal Agents (P Gubbins, Section Editor)

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

Authors: Brad Moriyama, Sameer Kadri, Stacey A. Henning, Robert L. Danner, Thomas J. Walsh, Scott R. Penzak

Published in: Current Fungal Infection Reports | Issue 2/2015

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Abstract

Voriconazole is an antifungal triazole that is the first-line agent for treatment of invasive aspergillosis. It is metabolized by CYP2C19, CYP2C9, and CYP3A4 and demonstrates wide interpatient variability in serum concentrations. Polymorphisms in CYP2C19 contribute to variability in voriconazole pharmacokinetics. Here, evidence is examined for the use of voriconazole therapeutic drug monitoring (TDM) and the role of CYP2C19 genotyping in voriconazole dosing. The majority of studies exploring the impact of voriconazole TDM on efficacy and safety have found TDM to be beneficial. However, most of these studies are observational, with only one being a randomized controlled trial. High-volume multicenter randomized controlled trials of TDM are currently not available to support definitive guidelines. There is a significant relationship in healthy volunteers between CYP2C19 genotype and voriconazole pharmacokinetics, but this association is markedly less visible in actual patients. While CYP2C19 genotype data may explain variability of voriconazole serum levels, they alone are not sufficient to guide initial dosing. The timeliness of availability of CYP2C19 genotype data in treatment of individual patients also remains challenging. Additional studies are needed before implementation of CYP2C19 genotyping for voriconazole dosing into routine clinical care.
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Metadata
Title
Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole
Authors
Brad Moriyama
Sameer Kadri
Stacey A. Henning
Robert L. Danner
Thomas J. Walsh
Scott R. Penzak
Publication date
01-06-2015
Publisher
Springer US
Published in
Current Fungal Infection Reports / Issue 2/2015
Print ISSN: 1936-3761
Electronic ISSN: 1936-377X
DOI
https://doi.org/10.1007/s12281-015-0219-0

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