Towards personalized medicine in antifungal treatment: combination of pharmacogenetics and pharmacokinetics

Abstract

Voriconazole is an antifungal agent used in aspergillosis and in fluconazole-resistant Candida spp. infections. Voriconazol is mainly metabolized by cytochrome 2C19 wich is highly polymorphic. A significant portion of patients fail to achieve therapeutic drug concentrations, with a consequently increased risk of therapeutic failure. In this work, the use of voriconazole in the real life clinical setting was studied and a HPLC method for the pharmacokinetic determination of voriconazole was developed. In addition, the factors of voriconazole pharmacokinetic variability were evaluated demonstrating the importance of CYP2C19 pharmacogenetics and pharmacokinetic drug-drug interactions.