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Case Studies

Using PBPK to Extrapolate Animal Tissue Concentrations to Humans

Background & Problem

An approved small molecule therapeutic had shown efficacy in numerous target organs of interest in clinical trials. The client wished to show that this efficacy was explained by high drug penetration into these tissues.

Our Solution

Mouse biodistribution data was collected. A physiological-based pharmacokinetic (PBPK) model was built using the physicochemical data of the drug compound and the pharmacokinetics information in mice, which was then extrapolated to humans by optimizing absorption and clearance to human plasma data. The PBPK model was used to predict human tissue concentrations in the various organs.


The PBPK model showed that at the therapeutic dose, drug concentration exceeds the in vitro EC50 in numerous target organs of interest. In addition, the model suggested tissue binding and eventual dissociation from target, which was consistent with the proposed mechanism of action for this drug.