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 that the efficiency of uptake by enterocytes depends on an inwardly directed proton gradient--dipeptides and beta-lactam antibiotics being cotransported along with hydrogen ion. This gradient is thought to result from the sodium-hydrogen (Na(+)-H+) exchanger located on the brush-border membrane. The aim of the present study was to assess the in vivo relevance 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 amiloride 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 present data seem to confirm the role of Na(+) -H+ exchange in the uptake of beta-lactams by the intestine and to support the indirect sodium dependence of this carrier system in vivo.
Westphal
J F
JF
Laboratory of Internal and Experimental Pathology, University Hospitals of Strasbourg, France.
Jehl
F
F
Brogard
J M
JM
Carbon
C
C
D000328:Adult; D000584:Amiloride / Q000494:pharmacology*; D000658:Amoxicillin / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D001682:Biological Availability; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D012016:Reference Values; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects* / Q000502:physiology
D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D000658:Amoxicillin