Using a developed and validated (adult) PBPK model for an in vivo probe substance, a pediatric PBPK model can be established for children by scaling physiology, clearance processes (as parameterized in the adult model) and age-dependent protein binding including the process specific variabilities.
For qualification purpose, during the translation of Adult PBPK to children the following assumptions and considerations were made:
- when scaling and adult model to children, it was assumed that the metabolism and excretion pathways are qualitatively the same in children as in adults.
- For qualification purpose, no further changes to any other input parameters (e.g., lipophilicity, intestinal permeability, solubility) were allowed during the simulations in children.
Regarding the age-dependencies of the relevant anthropometric (height, weight) and physiological parameters (blood flows, organ volumes, binding protein concentrations, hematocrit, cardiac output) in children was gathered from the literature and has been previously published [1]. The information was incorporated into PK-Sim® and was used as default values for the simulations in children.
The applied ontogeny and variability of active processes that are built-in into PK-Sim® for translation to children, are described in the publically available "PK-Sim® Ontogeny Database Version 7.3" [2] or otherwise referenced for the specific process.
"Type in here which ontogeny process(es) you wan to qualify e.g. Distribution and GFR"
e.g.
For the Qualification of the distribution and GFR elimination of compounds, the following probe substances were included:
[2] OSPSuite.Documentation/PK-Sim Ontogeny Database Version 7.3.pdf