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

  • Pharmacology and Pharmacodynamics of Antifungal Agents (P Gubbins, Section Editor)
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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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Acknowledgments

This work was supported in part by the intramural research program of the National Institutes of Health. The opinions expressed in this paper are the authors’ and do not reflect those of the National Institutes of Health (NIH) Clinical Center, NIH, Department of Health and Human Services, or the Federal government. Dr. Walsh is a Scholar of the Henry Schueler Foundation and a Scholar of Pediatric Infectious Diseases of the Sharpe Family Foundation. The assistance of Judith Welsh, NIH Library, Office of the Director for the library research is gratefully acknowledged.

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Conflict of Interest

Sameer Kadri, Stacey A. Henning, Robert L. Danner, and Scott R. Penzak declare that they have no conflict of interest.

Brad Moriyama owns a stock in Merck.

Thomas J. Walsh has received research grants from Novartis, Astellas, Merck, ContraFect, Pfizer, Cubist, Theravance, and consultancy fees from Vestagen, ICo Therapeutics, Inc., Trius, Sigma Tau, Astellas, and Drais Pharmaceuticals, ContraFect, Novartis, Pfizer, Methylgene, and Cubist.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Pharmacy Department, NIH Clinical Center, 10 Center Drive, Bethesda, MD, 20892, USA

    Brad Moriyama & Stacey A. Henning

  2. Critical Care Medicine Department, NIH Clinical Center, Bethesda, MD, USA

    Sameer Kadri & Robert L. Danner

  3. Transplantation-Oncology Infectious Diseases Program, Department of Medicine, Pediatrics, and Microbiology and Infectious Diseases, Weill Cornell Medical Center of Cornell University, New York, NY, USA

    Thomas J. Walsh

  4. Department of Pharmacotherapy, University of North Texas System College of Pharmacy, Fort Worth, TX, USA

    Scott R. Penzak

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  1. Brad Moriyama
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Correspondence to Brad Moriyama.

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This article is part of the Topical Collection on Pharmacology and Pharmacodynamics of Antifungal Agents

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Moriyama, B., Kadri, S., Henning, S.A. et al. Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole. Curr Fungal Infect Rep 9, 74–87 (2015). https://doi.org/10.1007/s12281-015-0219-0

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