Pediatric physiology in relation to the pharmacokinetics of monoclonal antibodies.

INTRODUCTION: Dose design for pediatric trials with monoclonal antibodies (mAbs) is often extrapolated from the adult dose according to weight, age, or body surface area. While these methods account for the size differences between adults and children, they do not account for the maturation of processes that may play a key role in the pharmacokinetics and/or pharmacodynamics of mAbs. With the same weight-based dose, infants and young children typically receive lower plasma exposures when compared to adults. Areas covered: The mechanistic features of mAb distribution, elimination, and absorption are explored in detail and literature-based hypotheses are generated to describe their age-dependence. This knowledge can be incorporated into a physiologically based pharmacokinetic (PBPK) modeling approach to pediatric dose determination. Expert opinion: As data from pediatric clinical trials become increasingly available, we have the opportunity to reflect on the physiologic drivers of pharmacokinetics, safety, and efficacy in children with mathematical models. A modeling approach that accounts for the age-related features of mAb disposition can be used to derive first-in-pediatric doses, design optimal sampling schemes for children in clinical trials and even explore new pharmacokinetic end-points as predictors of safety and efficacy in children.