WHICH TOOL IS THE BEST GUIDE OPTIMIZE THE VORICONAZOLE DOSAGE: THERAPEUTIC DRUG MONITORING OR CYTOCHROME P450 POLYMORPHISM?

Abstract

Voriconazole (VCZ) is the drug of choice for invasive aspergillosis (IA). However, narraow therapeutic range and variable pharmacokinetics can effect the success of the therapy. VCZ serum concentration is influenced by several factor including CYP450 polymorphisms primarily by CY2C19. Therapeutic drug monitoring (TDM) of VCZ is highly recommended to check adequate serum concentrations. Herein, we investigated the usefulness of detecting CYP450 polymorphism. Patients with hematological malignancies were included in the study.CYP450 polymorphisms which are responsible for metabolism of VCZ were investigated using RT-PCR. TDM of VCZ was peformed usingLC/MS/MS.11 patients were included in the study. Frequencies of CYP2C19 genotypes are 27% for intermediate metabolizer; 36% rapid metabolizer, 18% for ultra rapid metabolizer, 18% for normal metabolizer. Two patients experienced dose related side effects and one of these patient’s voriconazole blood concentration was supratherapeuticAlthough VCZ is the drug of choice for thetreatment of IA, the variabality of the pharmacokinetics can influence the success of therapy significantly. Therefore implementing the pharmacogenetic testing and therapeutic drug monitoring to clinical practice might help clinicians to provide improved care to patients and improve treatment outcomes.