An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables.

INTRODUCTION

When pediatric data are not available for a drug, allometric and other methods are applied to scale drug clearance across the pediatric age-range from adult values. This is applied when designing first-in-child studies, but also for off-label drug prescription.

AREAS COVERED

This review provides an overview of the systematic accuracy of allometric and other pediatric clearance scaling methods compared to gold-standard PBPK predictions. The findings are summarized in decision tables to provide guidance on the selection of appropriate pediatric clearance scaling methods for both novel drugs for which no pediatric data are available and existing drugs in clinical practice.

EXPERT OPINION

While allometric scaling principles are commonly used to scale pediatric clearance, there is no universal allometric exponent (i.e. 1, 0.75, or 0.67) that can accurately scale clearance for all drugs from adults to children of all ages. Therefore, pediatric scaling decision tables based on age, drug elimination route, binding plasma protein, fraction unbound, extraction ratio, and/or isoenzyme maturation are proposed to select the appropriate (allometric) clearance scaling method, thereby reducing the need for full PBPK-based clearance predictions. Guidance on allometric scaling when estimating pediatric clearance values is provided as well.