Effect of Cytochrome P450 2C19 Genotyping and Therapeutic Drug Monitoring on Efficacy and Toxicity of Voriconazole Therapy

Invasive fungal infections are a significant cause of morbidity and mortality in immunocompromised patients and voriconazole is often prescribed because of its potent activity. Treatment success of voriconazole therapy is highly dependent on maintaining therapeutic concentrations which is challenging due to the high inter- and intra-patient variability in drug exposure. The complex kinetics of voriconazole renders current manufacturersâ dosing guidelines ineffective. The variability in drug exposure observed in clinical settings has been linked to genetic polymorphisms in the cytochrome P450 2C19 gene, which encodes for the enzyme primarily responsible for voriconazole metabolism. Therapeutic drug monitoring has been found to increase efficacy of voriconazole treatment. However, there is still inconsistency and delay in getting patients to reach target voriconazole concentrations. The aim of this thesis is to examine if implementation of cytochrome P450 2C19 real-time genotyping as part of voriconazoleâ s existing dosing algorithm can improve clinical outcomes.M.Sc