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• W2034113556 abstract "Vigabatrin is an anti-epileptic drug substance. The oral bioavailability of vigabatrin is high (60-70%), however, little is known about the mechanism(s) mediating the intestinal absorption. The aim of the present study was to identify which solute carrier(s) are involved in the absorption of vigabatrin in Caco-2 cells, a cell culture model of the small intestinal epithelium. The uptake and transepithelial flux of vigabatrin was measured using an LC-MS method for quantification. Transepithelial transport of vigabatrin was shown to be proton-dependent and polarized in the apical-to-basolateral (A-B) direction. The A-B flux of vigabatrin had a saturable component and a passive component, indicating the presence of a carrier system in parallel with a passive permeability. The Michaelis constant, Km, of the transepithelial A-B flux of vigabatrin was estimated to be 32.8±7.4 mM (n=3-5), whereas the Km of the apical uptake was found to be 12.7±3.7 mM (n=3). The carrier-mediated transepithelial A-B flux of vigabatrin accounted for 80-95% (50.0-1.0mM) of the total A-B flux. The transepithelial A-B flux (as well as apical uptake) of vigabatrin was significantly decreased upon addition of substrates or inhibitors of the human proton-coupled amino acid transporter (hPAT1) to the apical solution. The present study indicates that the transepithelial A-B flux of vigabatrin is mainly mediated by hPAT1 in Caco-2 cells at dose-relevant concentrations." @default.
• W2034113556 created "2016-06-24" @default.
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• W2034113556 date "2014-01-01" @default.
• W2034113556 modified "2023-10-10" @default.
• W2034113556 title "The absorptive flux of the anti-epileptic drug substance vigabatrin is carrier-mediated across Caco-2 cell monolayers" @default.
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• W2034113556 doi "https://doi.org/10.1016/j.ejps.2013.08.034" @default.
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