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

J Pharm Pharmacol. 1987 Apr;39(4):272-7. doi: 10.1111/j.2042-7158.1987.tb06265.x.


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-beta-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 alpha-amino group in the side chain, suggesting transport through the dipeptide carrier system(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butanols
  • Cefixime
  • Cefotaxime / analogs & derivatives*
  • Cefotaxime / metabolism
  • Dose-Response Relationship, Drug
  • Hydrogen-Ion Concentration
  • Intestinal Mucosa / metabolism*
  • Kinetics
  • Male
  • Rats
  • Rats, Inbred Strains
  • Sodium / pharmacology
  • Solubility
  • Structure-Activity Relationship


  • Butanols
  • isobutyl alcohol
  • Cefixime
  • Sodium
  • Cefotaxime