Towards personalized medicine in antifungal treatmentcombination of pharmacogenetics and pharmacokinetics
- Blanco Dorado, Sara
- M.ª Jesús Lamas Díaz Director
- Manuel Campos Toimil Director
- Anxo Fernández Ferreiro Director
Universidade de defensa: Universidade de Santiago de Compostela
Fecha de defensa: 05 de xuño de 2020
- Olga Delgado Sánchez Presidente/a
- Arturo González Quintela Secretario
- Fernando Gutiérrez Nicolás Vogal
Tipo: Tese
Resumo
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.