Prediction from Permeabilities Through Caco-2 Cell Lines

Prediction from Permeabilities Through Caco-2 Cell Lines 

Caco-2 cell lines have been proposed by different authors as good substrates to study the permeability of drug candidates, especially if they can be actively effluxed to the intestine by MDR transporters. From our point of view this cellular line can 

The first step in this direction is to correlate the permeability values obtained in the Caco-2 cell lines (apical-basolateral direction, Pay) with the fraction of dose absorbed in vivo in rat For this proposal eight fluoroquinolones were assayed and the results found with Caco-2 cell lines were compared with those obtained in vivo in rat In the Caco-2 cell lines the permeability of the quinolones was evaluated at different initial concentration, in order to test for no linearities in the absorption process. For some of them, it was observed that a secretion system worked in the opposite direction to passive diffusion for this reason the permeability value used for the correlations, in the case of secretion, was the one obtained at the highest concentration of the quinolone, which corresponds to saturation of the secretion process. 

The equation fitted to the data was similar to the one used for the in situ data  

Where A. is a parameter of the fitting that has no equivalence with any physiological parameter, since the solutions are exposed to the membrane at infinite dose during the permeation assays. 

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The results are outlined in Fig. 4.7. As can be seen, the correlation is significant. Nevertheless, the bioavailability of the more hydrophilic compounds (norfloxacin, ciprofloxacin) is underestimated by their permeabilities through the Caco-2 cell line. The mean prediction error of this model is higher than the one obtained from in situ data (Table 4.2). 

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