Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/25487
Title: Intestinal transport of bis(12)-hupyridone in caco-2 cells and its improved permeability by the surfactant Brij-35
Authors: Yu, H
Hu, YQ
Ip, FCF
Zuo, Z
Han, YF 
Ip, NY
Keywords: Absorption
Bis(12)-hupyridone
Multidrug resistance- associated protein
Nonionic surfactant
P-glycoprotein
Issue Date: 2011
Publisher: Wiley-Blackwell
Source: Biopharmaceutics and drug disposition, 2011, v. 32, no. 3, p. 140-150 How to cite?
Journal: Biopharmaceutics and Drug Disposition 
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 μM. However, only apical efflux was observed in the directional transport studies for B12H below 88 μM (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 μM). Therefore, Brij-35 can be used as a potential enhancer to improve intestinal absorption of B12H for oral administration.
URI: http://hdl.handle.net/10397/25487
DOI: 10.1002/bdd.745
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