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

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.