Do Children Have the Same Vulnerability to Metabolic Drug-drug Interactions as Adults? A Critical Analysis of the Literature

Many drug–drug interactions (DDIs) in the pediatric population are managed based on data generated in adults. However, due to developmental changes in elimination pathways from birth to adolescence, and variable weight-adjusted dose of interacting drugs, the assumption of DDIs being similar in adults and pediatrics might not be correct. This study compares the magnitude of reported DDIs in pediatric and adult populations. A systematic literature review was undertaken to identify reports of DDIs in pediatric subjects. A total of 145 reports of DDIs were identified over the age range of birth to 20 years. The magnitude of DDIs for 24 drug pairs from 31 different pediatric studies could be assessed and compared with those in adults where corresponding data existed. The magnitude of the DDI, as measured by a relevant parameter (e.g., AUC, CL) in the presence and absence of inhibitor,were higher (>1.25-fold), similar (0.8- to 1.25-fold) or lower (<0.8-fold) than the corresponding ratio in adults in 10, 15, and 8 cases respectively. An age-related trend in the magnitude of DDIs could not be established. However, the study highlighted the clear paucity of the data in children younger than 2 years. Care should be exercised when applying the knowledge of DDIs from adults to children younger than 2 years of age.