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Absorption mechanisms of secondary aliphatic amines in rat colon and small intestine.

This study is intended to be a further and conclusive validation of the bihyperbolic model equation proposed by Plá-Delfina and Moreno to describe passive intestinal absorption mechanisms through the analysis of absorption-lipophilicity correlations for homologous series of xenobiotics and drugs. Secondary aliphatic amines, largely differing from previously tested substances, were selected as model compounds. Evidence is given which demonstrates that a minimum lipophilicity value exists for absorption in small intestine, instead of a maximum, as probabilistic theories predict. Moreover, bihyperbolic equation provides an excellent fit, with AIC figures up to -29. Aqueous pore absorption was small, presumably due to ionic interactions with pore charges (kp approximately 1.0 h-1), whereas membrane penetration was highly lucrative (km approximately 7.4 h-1), thus indicating that some part of the lipophilic ionic species is capable of penetrating "per se" the lipoidal membrane. As model predicts, bihyperbolic equation collapses to monohyperbolic for colonic absorption, where AIC figures up to -39 were found, with a km value of about 4.0 h-1. Membrane absorption efficiency was, surprisingly, similar in colon and small intestine for the tested solutes; it was attributed to the basic character of the compounds associated with working pH and ion absorption. This latter effect would deserve further investigation in oral sustained-release medication with basic drugs having similar pKa values.