Impact of CYP2C19 Phenotype and Drug-Drug Interactions on Voriconazole Concentration in Pediatric Patients

Voriconazole (VRC), a first-line agent for the treatment of invasive fungal infections, is mainly metabolized by human cytochrome P450 (CYP) 2C19. In this study, a retrospective analysis was performed to investigate the key factors that influence the plasma trough concentration ( ) of VRC, and an appropriate dosing regimen for pediatric patients was drafted subsequently. Overall, factors such as age, CYP2C19 phenotype, and combination medication with proton pump inhibitors accounted for 23.4% of variability in dose-normalized values of VRC by a multiple linear regression analysis. Dose-normalized values in the poor metabolizers (PMs) and intermediate metabolizers (IMs) were significantly higher than those in extensive metabolizers (EMs) ( 0.001). To achieve therapeutic for CYP2C19 ultrarapid metabolizers (UMs) or EMs, patients aged no more than 12 and more than 12 years required doses of 6.53 ± 2.08 and 3.95 ± 0.85 mg/kg of body weight twice daily ( 0.007). For CYP2C19 PMs or IMs, patients aged under 12 and over 12 years required doses of 5.75 ± 1.73 and 4.23 ± 0.76 mg/kg twice daily, respectively ( 0.019). Furthermore, coadministration of rifamycin sodium or omeprazole exhibited significant effects on VRC . Taken together, it is necessary to pay attention to the impact of CYP2C19 phenotype and drug-drug interactions to achieve optimal therapy.