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- W2099894316 abstract "Abstract The objective of the present study was to elucidate the mechanisms of intestinal transport of bis(12)‐hupyridone (B12H) to predict its oral bioavailability. The effect of the B12H concentration and the contribution of the drug efflux transporters, P‐glycoprotein (P‐gp or ABCB1) and multidrug resistance‐associated proteins (MRPs or ABCC) on B12H absorption were measured and evaluated using the human intestinal epithelial Caco‐2 cell monolayer in the presence of transporter inhibitors. The results indicated that B12H was absorbed in a dose‐dependent manner at concentrations ranging from 132 to 264 µ M . However, only apical efflux was observed in the directional transport studies for B12H below 88 µ M ( P app (AP‐to‐BL): virtually zero; P app (BL‐to‐AP): 1.591 ± 0.071 × 10 −5 cm s −1 ). P‐gp and mixed P‐gp/MRP inhibitors significantly increased the absorptive transport ( P app (AP‐to‐BL)) to 0.619 ± 0.018 × 10 −5 and 0.608 ± 0.025 × 10 −5 cm s −1 , respectively, while decreasing secretory transport ( P app (BL‐to‐AP)) by >75%. A multiple‐MRP inhibitor, probenecid, increased the P app (AP‐to‐BL) to 0.329 ± 0.015 × 10 −5 cm s −1 while decreasing the P app (BL‐to‐AP) by 50%. Another multiple‐MRP inhibitor, indomethacin, only modestly decreased the P app (BL‐to‐AP) by ∼30% and had no effect on the absorptive transport ( P app (AP‐to‐BL): virtually zero). In addition, the effect of various pharmaceutical excipients (e.g. Pluronic F‐68, Tween‐80 and Brij‐35) on B12H transport was determined and compared. Among them, Brij‐35 effectively enhanced B12H absorption at a concentration lower than its critical micelle concentration (CMC, 60 µ M ). Therefore, Brij‐35 can be used as a potential enhancer to improve intestinal absorption of B12H for oral administration. Copyright © 2011 John Wiley & Sons, Ltd." @default.
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- W2099894316 date "2011-01-27" @default.
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- W2099894316 title "Intestinal transport of bis(12)-hupyridone in Caco-2 cells and its improved permeability by the surfactant Brij-35" @default.
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- W2099894316 doi "https://doi.org/10.1002/bdd.745" @default.
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