Adjustment for Differences in Body Size PBPK Models

5 Adjustment for Differences in Body Size PBPK Models 

Extrapolation between species should ideally take into account metabolic routes, i.e., the absence or presence of metabolites, as well as the relative rate of formation of the individual metabolites. In PBPK models (Section 4.3.6), both aspects (nonlinearity, formation of active metabolites) are incorporated. This modeling technique uses compartments that correspond to actual tissues or tissue groups of the body. Size, blood flow, air flow, etc. are taken into account, in addition to specific compound-related parameters such as partition coefficients and metabolic rate data. Based on such studies, target-organ concentrations of active metabolites can be predicted in experimental animals and humans, thus providing the best possible basis for extrapolation (Feron et al. 1990). 

---