¹Laboratory of Internal and Experimental Pathology, Unit of Pharmacokinetics of the Institute of Bacteriology, University Hospitals of Strasbourg, Strasbourg, and the National Institute of Health and Medical Research, U13, University Hospital Xavier Bichat. Paris, France

Correspondence: Jean-Frédéric Westphal, MD, PhD, Ministère de la Santé, Agence Française du Médicament, Direction de l'Evaluation, 145, boulevard Anatole France, 93200 Saint-Denis, France.

Received 1 February 1994; Accepted 12 September 1994.

Abstract

Intestinal absorption of -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 -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 -lactams by the intestine and to support the indirect sodium dependence of this carrier system in vivo.