Population Pharmacokinetics in Pediatric Drug Development

Abstract

Pediatric product development initiatives in the United States have resulted in improved product labeling, increased identification of adverse events, and development of new pediatric formulations. However, a substantial number of pediatric trials have failed to establish either safety or efficacy, leading to an inability to label the product for use in children. An important consideration is drug dosing with resulting inadequate drug exposure, which was found to be a possible contributing factor to pediatric trial failures in nearly a quarter of failed pediatric drug development programs reviewed by the US Food and Drug Administration (FDA) between 2007 and 2014 [1]. A number of scientific tools are now being applied in pediatric drug development to improve pediatric dosing and increase the success rate of pediatric trials. Population pharmacokinetics (POPPK), broadly defined as the quantitative approach to describe pharmacokinetic (PK) data and identify and characterize sources of variability in drug disposition, is one such tool that has made a significant contribution to understanding PK and drug exposure linked to clinical outcomes in the pediatric patient population. POPPK is a robust tool that can handle sparse and unbalanced PK data, which is common in pediatric studies secondary to the logistical and ethical considerations of studying drugs and biologics in children. Additionally, the pediatric population is highly diverse with respect to body size, renal and metabolic maturation, and hormonal status, and the population approach can be used to understand how these factors impact variability in drug disposition and response. The objective of this chapter is to provide an overview of POPPK in pediatric drug development.