CYP2C19 Phenotype and Body Weight-Guided Voriconazole Initial Dose in Infants and Children after Hematopoietic Cell Transplantation
Takuto Takahashi, Maryam A. Mohamud, Angela R. Smith, Pamala A. Jacobson, Mutaz M. Jaber, Abeer Alharbi, James Fisher, Mark N. Kirstein
Abstract
< 0.05 for both). Our model performance for age <2 years was comparable to that for other age groups. Simulation of the final model suggested the following doses to attain target steady-state trough concentrations of 1.5 to 5.0 mg/liter for the CYP2C19 normal phenotype: 16 mg/kg (weight of <15 kg), 12 mg/kg (weight of 15 to 30 kg), or 10 mg/kg (weight of >30 kg); doses were 33 to 50% lower for CYP2C19 poor/intermediate phenotypes and 25 to 50% higher for CYP2C19 rapid/ultrarapid phenotypes. We propose a new starting-dose regimen, combined with therapeutic drug monitoring, for intravenous voriconazole therapy in children of all ages. Future studies should validate this dosing regimen.