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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.

Author information

1
Center for Pharmacometrics & Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.
2
Levine Cancer Institute, Department of Cancer Pharmacology, Charlotte, North Carolina, USA.
3
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
4
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.

Abstract

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.

PMID:
29315506
PMCID:
PMC6037619
[Available on 2019-11-01]
DOI:
10.1002/cpt.1012

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