Abstract
The purpose of this study was to clarify the competition and the mechanism of intestinal absorption of various cationic drugs by in situ and in vitro techniques. As model drugs, pralidoxime iodide (2-PAM) and several amine drugs were employed. Although the absorption of 2-PAM and 2-allyloxy-4-chloro-N-(2-diethylaminoethyl) benzamide hydrochloride (A. C. D. B.) became saturated when drug concentration increased, they might not be absorbed actively. Nine amine drugs including A. C. D. B. competitively inhibited the absorption of 2-PAM. Furthermore, the absorption of A. C. D. B. was similarly inhibited by one of the amine drugs. No physicochemical interaction as well as direct action on the membrane permeability were observed. Since A. C. D. B. did not affect the absorption of quinine and L-tryptophan, its effect is thought to be brought on the specified drugs. Inhibitory action of the amine drugs on the accumulation of 2-PAM to the gut wall and the uptake to the epithelial cells were operative. Since pharmacologic action of amine drugs is so varied and the drugs with opposite pharmacologic action inhibit 2-PAM absorption as well, it is supposed that the molecular structures which amine drugs have in common (phenylalkylamine) may relate to the inhibitory effect. Other cationic drugs having no such group did not affect the absorption of 2-PAM at all.
