What dose to give to a child
Adjusting the dose to the bodyweight of the child is common, but may not be the right solution as you may end up giving an overweight 2 year old the same dose as a lean 4 year old.
Giving the dose by Body Surface Area (BSA) may be even worse, as the equation that is most commonly used to calculate BSA was derived in 1916 with 9 individuals of which the youngest was 12 years old.
So what to do? We have applied physiologically-based pharmacokinetic models (PBPK) successfully to predict dose ranges for children in different age groups. These models take the maturation of the different processes related to drug absorption and elimination in a child into account and also allow for a different body composition as children have more water and less fat than adults. Depending on the absorption and elimination pathways as well as the physicochemical characteristics of the new molecule it can then be estimated what the potential behaviour of the drug would be in children at different ages.
The final dose finding for children has still to be done in clinical studies, but using the valuable information from PBPK models can narrow the dose range to be explored considerably and thereby reduce the number of children that will be exposed to a suboptimal dose in the testing period.