Advances in pharmacokinetic-pharmacodynamic modelling for pediatric drug development: extrapolations and exposure-response analyses

INTRODUCTION: Pharmacokinetic (PK)-Pharmacodynamic (PD) and exposure-response (E-R) modeling are critical parts of pediatric drug development. By integrating available knowledge and supportive data to support the design of future studies and pediatric dose selection, these techniques increase the efficiency of pediatric drug development and lowers the risk of exposing pediatric study participants to suboptimal or unsafe dose regimens. AREAS COVERED: The role of PK, PK-PD and E-R modeling within pediatric drug development and pediatric dose selection is discussed. These models allow investigation of the impact of age and bodyweight on PK and PD in children, despite the often sparse data on the pediatric population. Also discussed is how E-R analyses strengthen the evidence basis to support (full or partial) extrapolation of drug efficacy from adults to children, and between different pediatric age groups. EXPERT OPINION: Accelerated pediatric drug development and optimized pediatric dosing guidelines are expected from three future developments: (1) Increased focus on E-R modeling of currently approved drugs in children resulting in (novel) E-R modeling techniques and best practices, (2) increased use of real-world data for E-R (3) increased implementation of available population PK and E-R information in pediatric drug dosing guidelines.