title: Quantitative clinical pharmacology for size and age scaling in pediatric drug development: A systematic review.
abstract: The establishment of drug dosing in children is often hindered by the lack of actual pediatric efficacy and safety data. To overcome this limitation, scaling approaches are frequently employed to leverage adult clinical information for informing pediatric dosing. The objective of this review is to provide a comprehensive overview of the different scaling approaches used in pediatric pharmacotherapy as well as their proper implementation in drug development and clinical use. We will start out with a brief overview of the current regulatory requirements in pediatric drug development, followed by a review of the most commonly employed scaling approaches in increasing order of complexity ranging from simple body weight-based dosing to physiologically-based pharmacokinetic (PBPK) modeling approaches. Each of the presented approaches has advantages and limitations, which will be highlighted throughout the course of the review by the use of clinically-relevant examples. The choice of the approach employed consequently depends on the clinical question at hand and the availability of sufficient clinical data. The main effort while establishing and qualifying these scaling approaches should be directed towards the development of safe and effective dosing regimens in children rather than identifying the best model, ie models should be fit for purpose.
authors.affiliation: Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Lake Nona (Orlando), FL, USA.
authors.forename: Tanay S
authors.initials: TS
authors.lastname: Samant
authors.affiliation: Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Lake Nona (Orlando), FL, USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Mangal
authors.affiliation: Simulations Plus, Inc., Lancaster, CA, USA.
authors.forename: Viera
authors.initials: V
authors.lastname: Lukacova
authors.affiliation: Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Lake Nona (Orlando), FL, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schmidt
mesh_terms: D000367:Age Factors; D049628:Body Size; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D010601:Pharmacology, Clinical / Q000379:methods*
keywords: allometric scaling; pediatric drug development; physiologically-based pharmacokinetic modeling