Apparent Component Approach models

Important limitations of the PBPK approach are realized for class 3 and 4 compounds with significant active distribution/absorption processes, where biliary elimination is a major component of the elimination process or where the assumptions of flow-limited distribution and well mixed compartments are not valid and permeability-limited distribution is apparent. These drawbacks could be addressed by the addition of permeability barriers for some tissues and by the incorporation of a more complex liver model which addresses active uptake into the liver, active efflux into the bile, biliary elimination and enterohepatic recirculation. However, this improvement to current methodologies requires the availability of the appropriate input data for quantification of the various processes involved as well as validation of the corresponding in vitro to in vivo scaling approaches. 

From this modelling approach it seems that the combined surface difiusion and activated gas translational difiusion can describe the observed single component permeation behaviour. The interpretation for the latter type of diffusion is not well-crystallized at present. It might have to do with an increasing deformation of the silicalite-1 structure with increasing temperature that causes this apparently activated process. This aspect has not been considered up to now, the silicalite-1 has been considered as a rigid structure. 

In conclusion, the present approach to surface tension components has some apparent similarities with the vOCG model [4-6,28] but, in essence, it is a drastically different approach. The key feature is that it provides with a sound basis for the interactions dictating interfacial phenomena, which is fully compatible with the picture we have about intermolecular interactions from quantum chemical calculations. The new approach has not been tested extensively yet, but the tests of this woik are indicating a rather satisfactory agreement with experiment. Work is underway in our laboratory toward a more extensive testing of the new approach against experimental data. 

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