I am trying to build a PK-model for an extended release formulation by combining a release model based on biorelevant dissolution testing and a PK model on an immediate release formulation.
-I was able to achieve a good fit for in-vitro release data and IR PK data individually
-Trying to combine in vitro release data with an IR PK model results in a decent curve shape and a good fit for initial plasma levels of the ER formulation, however later plasma levels are over-predicted. My interpretation is that colonic absorption is slower than absorption from the small intestines, resulting in this discrepancy.
-I would like to explore if the model could be improved by using different absorption characteristics (Ka) for the small intestines and the colon.
=>Is there a way to model a change of absorption constant (Ka) at a specific time point (or more preferably having this time point as a fitted parameter)?