Prediction of Clearance in Children from Adults Following Drug-Drug Interaction Studies: Application of Age-Dependent Exponent Model

Background and Objective Pharmacokinetic drug-drug interaction (DDI) studies are conducted in adult subjects during drug development but there are limited studies that have characterized pharmacokinetic DDI studies in children. The objective of this study was to evaluate if the DDI clearance values from adults can be allometrically extrapolated from adults to children. Methods Fifteen drugs were included in this study and the age of the children ranged from premature neonates to adolescents (30 observations across the age groups). The age-dependent exponent (ADE) model was used to predict the clearance of drugs in children from adults following DDI studies. Results The prediction error of drug clearances following DDIs in children ranged from 4 to 67%. Of 30 observations, 17 (57%) and 27 (90%) observations had a prediction error <= 30% and <= 50%, respectively. Conclusion This study indicates that it is possible to predict the clearance of drugs with reasonable accuracy in children from adults following DDI studies using an ADE model. The method is simple, robust, and reliable and can replace other complex empirical models.