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Comparison of ceftibuten transport across Caco‐2 cells and rat jejunum mounted on modified ussing chambers
Author(s) -
Me R.M.,
Barr W.H.
Publication year - 2003
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.366
Subject(s) - ussing chamber , paracellular transport , chemistry , jejunum , mannitol , transcellular , small intestine , biophysics , passive transport , biochemistry , permeability (electromagnetism) , membrane , in vitro , biology
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 m m . The net flux of mannitol and ceftibuten was higher across rat jejunum compared with Caco‐2 cells. At a donor concentration of 0.25 m m , 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 m m ceftibuten across Caco‐2 cells. Benzoic acid and adipic acid also inhibited transcellular transport of ceftibuten. At a donor concentration of 0.25 m m , 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 m m . In the concentration range 0.25–10 m m , ceftibuten is predominantly transported by paracellular mechanisms across rat jejunum and a mixture of active and passive transport across Caco‐2 cells. Copyright © 2003 John Wiley & Sons, Ltd.