Dose Scaling and Extrapolation Across Age Groups

Abstract

This paper considers how the logic of cross-species dose scaling applies (or does not apply) when extrapolating among differently sized humans, and specifically, when extrapolating to children. Scaling children's doses by a power of body weight predicts that they would be less sensitive to chemicals than adults, owing to faster clearance. Possible countervailing factors, however, are the role of quicker pharmacodynamic processes, differences between interspecific and ontogenetic allometry, and the complex role of inherent differences in the metabolism and physiological system of immature bodies, the last leading to uncertainty in extrapolation but not necessarily to systematic sensitivity among children. The issue of scale per se does not appear to provide a basis for positing a systematically greater sensitivity of children to toxic substances

Keywords:

• pharmacokinetics
• pharmacodynamics
• interspecies scaling
• children's risk
• uncertainty factors.