COMPARED EFFECTS OF SYNTHETIC AND NATURAL BILE-ACID SURFACTANT ON XENOBIOTIC ABSORPTION .2. STUDIES WITH SODIUM GLYCOCHOLATE TO CONFIRM A HYPOTHESIS

The effects of sodium glycocholate (SGC) on the intestinal absorption of drug-related xenobiotics are investigated; on the basis of previously established absorption/partition relationships. Six phenylalkylcarboxylic acids, closely related to nonsteroid anti-inflammatory drugs in structure and constituting a true homologous series, were used as test compounds through an in situ rat gut technique, using the whole colon as nonspecialized absorption membrane model, Whereas the synthetic surfactants (i.e., polysorbates and laurylsulphates) at the critical micelle concentration have been shown to disrupt the aqueous boundary layer adjacent to the membrane, SGC does not; in contrast, it reinforces its limiting effect on solute diffusion, thus leading to a poorer absorption of the compounds as their lipophilicity increases. On the other hand, at supramicellar concentrations, the micelle solubilizing effect of SGC for the compounds is incomparably lower than that found for synthetics, even in the presence of mixed micelles with lecithin. These results, in conjunction with previous observations, seem to indicate that as far as xenobiotic absorption is concerned, synthetics and natural bile acid surfactants behave as entirely different biopharmaceutical species.