Absorption-partition relationships for true homologous series of xenobiotics as a possible approach to study mechanisms of surfactants in absorption. II. Aromatic amines in rat small intestine

Abstract

The previously proposed approaches in order to interpret the mechanisms elicited by the nonionic surfactant polysorbate 80 in the colonic absorption of 4-alkylanilines are extended here to the absorption of the same compounds in the rat small intestine, where compound behaviour seems to be complicated by the existence of a pore diffusion pathway, simultaneous with membrane absorption. Globally considered, the effects of surfactant in the intestinal absorption of anilines relative to the behaviour of these compounds in free solution are much less evident than in colon for low-molecular-weight hydrophilic compounds of the series, for which pore absorption is highly operative, but, as lipophilicity and molecular weight increase, the effects of surfactant become more and more significant, showing a close resemblance with those observed in colon. In the absence of surfactant, a bihyperbolic correlation can be established between intestinal absorption rate constants of anilines and partition constants. On this basis, the apparently complex absorption-partition correlations found in the presence of surfactant at the critical micelle concentration are explained here by assuming that pore absorption of the compounds is virtually unaffected by surfactant at this concentration, contrarily to that which occurs with membrane permeation, for which the same effects as found on bulk rate constants in colon are observed; a clearly linear and double-logarithmic correlation can be established between membrane absorption rate constants and partition constants, thus indicating that two main effects of the surfactant are elicited i.e. the removal of the limiting effect of the aqueous diffusion layer adjacent to the membrane, and an increased membrane polarity. At 5% surfactant concentration in the perfusion fluid, clearly supramicellar, correlations between membrane intestinal absorption rate constants and partition constants become, as occurred with bulk constants in colon, bilinear, due to the multiple-phase equilibrium arising from micellar solubilization of anilines; pore absorption constants are greatly reduced at this concentration, but correlate well with partition constants through an inverse hyperbolic equation as in the former cases. Biopharmaceutical implications of these observations are briefly discussed.