Correlation between cell- and tissue-based in vitro models for drug permeability screening with in vivo situation: modeling and functional extrapolation

The usefulness of an in vitro permeability assay is directly related to its ability to capture the fundamental aspects of the drug passage through in vivo membranes. Various approaches can be undertaken in order to establish the connection between the in vitro permeability and some, more or less directly related, in vivo measure of drug permeability. This chapter outlines some strengths and limitations of the direct empirical correlations between in vitro and in vivo data. Because permeability is often only a part of a more complex absorption process, it also summarizes the use of physiologically based pharmacokinetic models as a tool to further enlighten the physiological mechanism underlying the overall mechanism of in vivo permeability of drugs.