The effect of ontogeny in drug-metabolizing enzymes on pediatric pharmacokinetics is poorly predicted. Voriconazole, a potent antifungal, is cleared predominantly via oxidative metabolism and exhibits vastly different pharmacokinetics between adults and children. A physiologically based pharmacokinetic (PBPK) model was developed integrating hepatic in vitro metabolism data with physiologic parameters to predict pharmacokinetic parameters of voriconazole in adult and pediatric populations.