ISSN:
1573-904X
Schlagwort(e):
oral β-lactam antibiotic
;
cephalexin
;
ACE inhibitor
;
quinapril
;
peptide carrier system
;
proton-gradient
;
intestinal absorption
;
Caco-2
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Chemie und Pharmazie
Notizen:
Abstract 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.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1023/A:1016247523311
Permalink