The MITIGATE project will develop and implement a physiologically based pharmacokinetic (PBPK) model for the simulation and prediction of human biodistribution and absorbed doses using mice biodistribution data. The simulation and prediction of human biodistribution could be offered as a service or developed into a stand-alone software.
As a first step, the model will use murine biokinetic data of tumour, kidney, liver and spleen, together with the amount of injected substance and activity, as input.
After determining the adjustable fitting parameters for the corresponding xenograft in a second step, the model parameters, e.g. blood flows and organ masses, are changed from mouse to human. For this human model, the user can add the receptor density and volume of the human tumour as additional parameter, and simulate the human biodistribution.
The output, the time-integrated activity coefficients, can then be used to calculate the expected absorbed doses. Different quantities of injected amounts and activities can be simulated to determine a suitable first-in-man-dosage.
