Mechanisms of Transport of Quinapril in Caco-2 Cell Monolayers: Comparison with Cephalexin

Ming Hu, Lixing Zheng, Jiyue Chen, Lijuan Liu, Yanping Zhu, Anne H. Dantzig, Robert E. Stratford

Research output: Contribution to journalArticle

48 Scopus citations


Purpose. To determine the transport mechanisms of quinapril and cephalexin in Caco-2 cell monolayers, a cell culture model of the human small intestinal epithelium. Methods. Uptake, transepithelial transport and intracellular accumulations of these two drugs were measured using Caco-2 cell monolayers grown onto Millicells and magnetically stirred diffusion chambers. Results. Transepithelial transport, apical (AP) uptake and intracellular accumulation of both drugs depended on the maintenance of a transepithelial proton gradient and temperature of the medium. However, quinapril transport and accumulation, which did not display a maximum at approximately pH 6, was more sensitive to proton gradient change, whereas cephalexin transport was more sensitive to concentration change (range 0.5-5 mM). In addition, quinapril (1 mM) transport was decreased significantly (p<0.05) by 10 mM cephalexin, loracarbef, Gly-Pro and Phe-Pro, but not by enalapril; whereas cephalexin (0.1 mM) transport was decreased significantly (p<0.05) by all four compounds. Similarly, AP quinapril (1 mM) uptake was also decreased by 10 mM loracarbef, Gly-Pro, cephalexin, and enalapril, but these inhibitory effects (20-50%) were quantitatively less than their inhibitory effects on cephalexin uptake (50-90%). Finally, the AP uptake of quinapril was also significantly (p<0.05) inhibited by FCCP (10 µg/ml), amiloride (0.5 mM), DEP (0.5 mM), and staurosporine (5 nM). Conclusions. The transport of quinapril in the Caco-2 cells is via a combination of the carrier-mediated proton gradient-dependent peptide transporter and passive diffusion.

Original languageEnglish (US)
Pages (from-to)1120-1125
Number of pages6
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Issue number8
StatePublished - Aug 1995
Externally publishedYes


  • ACE inhibitor
  • Caco-2
  • cephalexin
  • intestinal absorption
  • oral β-lactam antibiotic
  • peptide carrier system
  • proton-gradient
  • quinapril

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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