Sodium glycocholate transport across Caco-2 cell monolayers, and the enhancement of mannitol transport relative to transepithelial electrical resistance.
Ideally, the amount of enhancer remaining at the donor side during an in vitro transport study should be known, in order to know the true enhancer concentration during a permeability study. The purpose of the present study is to estimate the flux of the enhancer, sodium glycocholate (GC), through Caco-2 cell monolayers, and to study the effect of various enhancer concentrations on the permeability of GC itself, the permeability of mannitol and the transepithelial electrical resistance (TEER). Apical to basolateral permeability was measured with various concentrations 0.50% (10.2mM), 0.75% (15.5mM) and 1.00% (20.5mM) of GC. The GC permeabilities (Papp) were 4.7+/-1.1, 12.8+/-2.8 and 25.8+/-4.3 (x10(-7)cms(-1)), respectively. Mannitol transport changed accordingly with the Papp; 8.5+/-0.8, 9.9+/-2.7, 20.4+/-2.8 and 31.0+/-4.9 (x10(-7)cms(-1)) for GR, 0.50, 0.75 and 1.00% GC, respectively, with a TEER after 120min, relative to initial, of 86+/-6, 77+/-10, 61+/-11 and 49+/-7%. In conclusion a low and concentration-dependent permeability was found for GC across the Caco-2 cells. Mannitol transport increased and TEER decreased accordingly with increasing GC concentrations. TEER decreased in less than 10min to a certain level, without further reduction in a 120min period, indicating that the enhancer effect is momentarily, rather than time-dependent. The apical GC concentration and enhancer effect may be considered well defined during the experiment, due to the observed low permeability of GC.
Lindhardt
Karsten
K
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, 2100, Copenhagen, Denmark.
Bechgaard
Erik
E
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism*; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D006000:Glycocholic Acid / Q000493:pharmacokinetics*; D006801:Humans; D008353:Mannitol / Q000493:pharmacokinetics*
D008353:Mannitol; D006000:Glycocholic Acid