Pharmaceutical Research

, Volume 16, Issue 1, pp 55–61

Intestinal Transport of β-Lactam Antibiotics: Analysis of the Affinity at the H+/Peptide Symporter (PEPT1), the Uptake into Caco-2 Cell Monolayers and the Transepithelial Flux

  • Beate Bretschneider
  • Matthias Brandsch
  • Reinhard Neubert

DOI: 10.1023/A:1018814627484

Cite this article as:
Bretschneider, B., Brandsch, M. & Neubert, R. Pharm Res (1999) 16: 55. doi:10.1023/A:1018814627484


Purpose. This study on the intestinal transport of β-lactam antibiotics was undertaken to investigate the correlation between cellular transport parameters and the bioavailability.

Methods. Transport of 23 β-lactam antibiotics was characterized by measuring their ability to inhibit the uptake of glycylsarcosine into Caco-2 cells, their uptake into the cells and their total flux across the cell monolayers.

Results. Ceftibuten and cyclacillin were recognized by PEPT1 with affinity constants comparable to those of natural dipeptides (Ki = 0.3 and 0.5 mM, respectively). Cefadroxil, cefamandole, cephradine, cefaclor, cefuroxime-axetil, cefixime, cephalotin, cephalexin and ampicillin also interacted with PEPT1 (Ki = 7-14 mM). In contrast, cefapirin, cefodizime, cefuroxime, cefmetazole, ceftazidime, benzyl-penicillin, ceftriaxone, cefpirome, cefotaxime, cefepime, cephaloridine and cefsulodin displayed no affinity to the transport system (Ki > 20 mM). The uptake into the cells and the transepithelial flux was highest for those β-lactam antibiotics, which showed the strongest inhibition of [14C]Gly-Sar transport (p < 0.0001). Exceptions were cefuroxim-axetil and cephalotin.

Conclusions. The probability of oral bioavailability for β-lactam antibiotics is mainly determined by their affinity to PEPT1. A threshold Ki value of 14 mM with respect to Gly-Sar uptake is required.

PEPT1 peptide transport β-lactam antibiotics Caco-2 cells cephalosporins penicillins 

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Beate Bretschneider
    • 1
  • Matthias Brandsch
    • 2
  • Reinhard Neubert
    • 1
  1. 1.Department of Pharmacy, Institute of Pharmaceutics and BiopharmaceuticsMartin-Luther-University Halle-WittenbergHalleGermany
  2. 2.Biozentrum of the UniversityHalleGermany