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Amoxicillin intestinal absorption reduction by amiloride: Possible role of the Na + ‐H + exchanger
Author(s) -
Westphal JeanFrédéric,
Jehl François,
Brogard JeanMarie,
Carbon Claude
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90150-7
Subject(s) - amiloride , chemistry , bioavailability , sodium–hydrogen antiporter , in vivo , absorption (acoustics) , pharmacology , sodium , pharmacokinetics , amoxicillin , biophysics , biochemistry , antibiotics , medicine , biology , materials science , microbiology and biotechnology , organic chemistry , composite material
Intestinal absorption of β‐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 β‐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 β‐lactams by the intestine and to support the indirect sodium dependence of this carrier system in vivo. Clinical Pharmacology & Therapeutics (1995) 57 , 257–264; doi: