Physiologically Based Pharmacokinetic Modeling in Pediatric Drug Development: A Clinician’s Request for a More Integrated Approach

Abstract EN

With great interest we read the paper of Khalil and Läer on the concepts of physiologically based pharmacokinetic (PBPK) modeling and its applications to pediatric drug development [1].

The authors clearly described the methodology, applications, and limitations of PBPK models in pediatric drug development [1].

In essence, PBPK models hold the promise to design and perform a pediatric study based on “a well-educated guess” to paraphrase what the authors refer to as “confirmatory” instead of “exploratory” approach.

The approach described by the authors hereby mainly reflects what we would like to describe as a “top-down (from model to clinical observations)” concept: based on the available knowledge on developmental anatomy and physiology, a PBPK model is developed, undergoes validation, and will subsequently facilitate pediatric studies [1].

We would like to further challenge research groups active in the field of PBPK modeling not to get too disconnected from the “in vivo” world of pediatric developmental pharmacology and also consider what we would like to describe as a “bottom-up (from clinical observations to model)” concept: from compound specific observations to mechanism-based models [2–5].

It is our strong opinion that active comparison between PBPK and mechanism based models using the same in vivo datasets can be helpful to further improve clinical care but also provides guidance for more focused studies on aspects of developmental physiology.