Saturable uptake of cefixime, a new oral cephalosporin without an α‐amino group, by the rat intestine

The mechanism of intestinal uptake of cefixime, a new oral cephalosporin antibiotic, has been examined using the everted jejunum of rats. The initial uptake rates were apparently pH‐dependent with the maximum rate at pH 5.0 and a 3‐fold reduction at pH 7.0. The uptake at pH 5.0 followed mixed‐type kinetics involving saturable and non‐saturable processes in a manner similar to that for several amino‐β‐lactam antibiotics. Cefixime uptake was inhibited significantly by 20 mM permeants such as cyclacillin, cephradine, benzylpenicillin, propicillin, glycyl‐L‐proline and glycyl‐glycine. Replacement of Na+ in the medium with choline produced a slight but significant inhibition of cefixime uptake. In spite of the absence of significant inhibition by the amino acids glycine and proline, the dipeptide, glycyl‐L‐proline in Na+‐free medium showed a marked inhibitory effect. The inhibition kinetics of cefixime uptake by glycyl‐L‐proline and cyclacillin were consistent with competitive‐type inhibition. This study provides the first evidence of saturable intestinal uptake of a cephem antibiotic without an α‐amino group in the side chain, suggesting transport through the dipeptide carrier system(s). 1987 Royal Pharmaceutical Society of Great Britain