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Clin Pharmacol Ther. 2018 Nov;104(5):957-965. doi: 10.1002/cpt.1012. Epub 2018 Feb 13.

Optimization of Voriconazole Therapy for the Treatment of Invasive Fungal Infections in Adults.

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Center for Pharmacometrics & Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.
Levine Cancer Institute, Department of Cancer Pharmacology, Charlotte, North Carolina, USA.
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.


Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using a drug monitoring approach, which relies on attainment of steady-state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5-7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model-based approach to predict doses that can maximize the net benefit (probability of efficacy-probability of adverse events) and ensure therapeutic concentrations, early on during treatment. The label-recommended 200 mg voriconazole dose resulted in attainment of targeted concentrations in ≥80% patients in the case of Candida spp. infections, as compared to only 40-50% patients, with net benefit ranging from 5.8-61.8%, in the case of Aspergillus spp. infections. Voriconazole doses of 300-600 mg were found to maximize the net benefit up to 51-66.7%, depending on the clinical phenotype (due to CYP2C19 status and pantoprazole use) of the patient and type of Aspergillus infection.

[Available on 2019-11-01]

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