PHARMACOKINETIC ANALYSIS OF THE ABSORPTION ENHANCING ACTION OF DECANOIC ACID AND ITS DERIVATIVES IN RATS

The enhancing action of decanoic acid (C10) and its derivatives on muc osal absorption of phenolsulfonphthalein (PSP) in the jejunum or colon was analyzed using pharmacokinetics in rats. After administration of a solution containing PSP and an enhancer [C10, 2-hydroxydecanoic acid (2-OHC10), or 3-hydroxydecanoic acid (3-OHC10)] into the jejunal or c olonic loop, the amounts of PSP and enhancer remaining in the loop and /or plasma PSP concentration were determined periodically. 2-OHC10 exh ibited a greater absorption enhancing potency than C10, while 3-OHC10 was less effective. Disappearance of residual PSP from the loop ceased after complete absorption of the enhancer. The enhancer-induced disap pearance rate constant of PSP correlated well with the product of the enhancer disappearance rate and its capacity to sequester calcium ions . In conclusion, the enhancement of PSP mucosal absorption by C10 and its derivatives is consistent with a pharmacokinetic model, assuming t hat the enhanced membrane permeability of PSP depends on the enhancer disappearance kinetics from the loop and its calcium ion sequestration capacity.