AMOXICILLIN INTESTINAL-ABSORPTION REDUCTION BY AMILORIDE - POSSIBLE ROLE OF THE NA-H+ EXCHANGER()

Intestinal absorption of beta-lactam antibiotics has been shown to use the dipeptide carrier system, In vitro experiments have established t hat the efficiency of uptake bp enterocytes depends on an inwardly dir ected proton gradient-dipeptides and beta-lactam antibiotics being cot ransported along with hydrogen ion. This gradient is thought to result from the sodium-hydrogen (Na+-H+) exchanger located on the brush-bord er membrane, The aim of the present study was to assess the in vivo re levance of these data in humans by examining the effect of amiloride, a well-known inhibitor of the Na+-H+ exchanger, on the bioavailability of amoxicillin in eight healthy volunteers, The results show that ami loride reduces significantly amoxicillin absorption rate (mean time to maximum concentration increases from 1.0 to 1.6 hours, p < 0.05) and absolute bioavailability (by 27%, p < 0.01) and that amiloride-induced inhibition of the intestinal Na+-H+ exchange could be associated with an additional inhibitory effect on (Na/K)-ATPase activity, The presen t data seem to confirm the role of Na+-H+ exchange in the uptake of be ta-lactams by the intestine and to support the indirect sodium depende nce of this carrier system in vivo.