Comparison of ceftibuten transport across Caco-2 cells and rat jejunum mounted on modified Ussing chambers.
Ceftibuten uptake into Caco-2 cells and intestinal brush border membrane vesicles is mediated by the dipeptide transport system (PEPT1). The apical to basolateral transport characteristics of ceftibuten across Caco-2 cells and rat jejunum mounted on a modified Ussing chamber was examined. Mannitol was used as a paracellular marker along with trans-epithelial electrical resistance (TEER) for monitoring tight junction permeability. Transport across Caco-2 cells and rat jejunum mounted on a modified Ussing chamber was linear across the concentration range 0.25-10 mM. The net flux of mannitol and ceftibuten was higher across rat jejunum compared with Caco-2 cells. At a donor concentration of 0.25 mM, ceftibuten transport across Caco-2 cells was found to be pH dependent. Glycyl proline, a dipeptide, and 2,4- dinitrophenol, an energy poison, caused a reduction in the permeability of 0.25 mM ceftibuten across Caco-2 cells. Benzoic acid and adipic acid also inhibited transcellular transport of ceftibuten. At a donor concentration of 0.25 mM, passive paracellular transport accounts for about 60% and the active carrier mediated mechanism accounts for about 40% of ceftibuten transport across Caco-2 cells. None of the inhibitors however, had a significant effect on ceftibuten transport across rat jejunum mounted on a modified Ussing chamber at a donor concentration of 0.25 mM. In the concentration range 0.25-10 mM, ceftibuten is predominantly transported by paracellular mechanisms across rat jejunum and a mixture of active and passive transport across Caco-2 cells.
Menon
R M
RM
Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA. rajeev.menon@richmond.ppdi.com
Barr
W H
WH
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells; D000077722:Ceftibuten; D002511:Cephalosporins / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002511:Cephalosporins; D000077722:Ceftibuten