Transport mechanism of cephalexin in isolated hepatocytes

J Pharmacobiodyn. 1987 Nov;10(11):632-8. doi: 10.1248/bpb1978.10.632.


By using isolated rat hepatocytes, the mechanism of uptake of a zwitterionic beta-lactam antibiotic, cephalexin, was clarified. The uptake followed the combination of saturable carrier-mediated and nonsaturable first-order rate processes. The kinetic parameters were estimated as follows (mean +/- SD): maximum uptake rate (Vmax), 2.28 +/- 0.24 nmol/min/mg of protein; Michaelis constant (Kt), 6.28 +/- 0.31 mM and first-order rate constant (kd), 0.11 +/- 0.012 nmol/min/mg of protein/mM. There was no inhibitory effect by amino acids, dipeptides or organic cations, whereas an organic anion, probenecid, markedly inhibited the hepatic uptake of cephalexin. Several beta-lactam antibiotics including zwitterionic and anionic derivatives inhibited cephalexin uptake significantly. The inhibition kinetics revealed that benzylpenicillin and the stereo-isomer l-cephalexin competitively inhibited cephalexin uptake. Furthermore, the efflux of cephalexin from the cells was stimulated by adding benzylpenicillin in the extracellular medium. These results demonstrated that all beta-lactam antibiotics have a common transport system with an organic anion such as probenecid, irrespective of their ionic charges, though a cationic charge on the molecule is less advantageous for being recognized by the carrier system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology
  • Animals
  • Anions / pharmacology
  • Anti-Bacterial Agents / metabolism
  • Cations / pharmacology
  • Cells, Cultured
  • Cephalexin / metabolism*
  • Cephalexin / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Dipeptides / pharmacology
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Rats
  • Rats, Inbred Strains


  • Amino Acids
  • Anions
  • Anti-Bacterial Agents
  • Cations
  • Dipeptides
  • Cephalexin