{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T23:59:21Z","timestamp":1778716761304,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,1,27]],"date-time":"2011-01-27T00:00:00Z","timestamp":1296086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The objective of the present study was to elucidate the mechanisms of intestinal transport of bis(12)\u2010hupyridone (B12H) to predict its oral bioavailability. The effect of the B12H concentration and the contribution of the drug efflux transporters, P\u2010glycoprotein (P\u2010gp or ABCB1) and multidrug resistance\u2010associated proteins (MRPs or ABCC) on B12H absorption were measured and evaluated using the human intestinal epithelial Caco\u20102 cell monolayer in the presence of transporter inhibitors. The results indicated that B12H was absorbed in a dose\u2010dependent manner at concentrations ranging from 132 to 264\u2009\u00b5<jats:sc>M<\/jats:sc>. However, only apical efflux was observed in the directional transport studies for B12H below 88\u2009\u00b5<jats:sc>M<\/jats:sc>(<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>(AP\u2010to\u2010BL): virtually zero;<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>(BL\u2010to\u2010AP): 1.591 \u00b1 0.071 \u00d7 10<jats:sup>\u22125<\/jats:sup>\u2009cm\u2009s<jats:sup>\u22121<\/jats:sup>). P\u2010gp and mixed P\u2010gp\/MRP inhibitors significantly increased the absorptive transport (<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>(AP\u2010to\u2010BL)) to 0.619 \u00b1 0.018 \u00d7 10<jats:sup>\u22125<\/jats:sup>and 0.608 \u00b1 0.025 \u00d7 10<jats:sup>\u22125<\/jats:sup>\u2009cm\u2009s<jats:sup>\u22121<\/jats:sup>, respectively, while decreasing secretory transport (<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>(BL\u2010to\u2010AP)) by &gt;75%. A multiple\u2010MRP inhibitor, probenecid, increased the<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>(AP\u2010to\u2010BL) to 0.329 \u00b1 0.015 \u00d7 10<jats:sup>\u22125<\/jats:sup>\u2009cm\u2009s<jats:sup>\u22121<\/jats:sup>while decreasing the<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>(BL\u2010to\u2010AP) by 50%. Another multiple\u2010MRP inhibitor, indomethacin, only modestly decreased the<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>(BL\u2010to\u2010AP) by \u223c30% and had no effect on the absorptive transport (<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>(AP\u2010to\u2010BL): virtually zero). In addition, the effect of various pharmaceutical excipients (e.g. Pluronic F\u201068, Tween\u201080 and Brij\u201035) on B12H transport was determined and compared. Among them, Brij\u201035 effectively enhanced B12H absorption at a concentration lower than its critical micelle concentration (CMC, 60\u2009\u00b5<jats:sc>M<\/jats:sc>). Therefore, Brij\u201035 can be used as a potential enhancer to improve intestinal absorption of B12H for oral administration. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.745","type":"journal-article","created":{"date-parts":[[2011,1,27]],"date-time":"2011-01-27T06:15:58Z","timestamp":1296108958000},"page":"140-150","source":"Crossref","is-referenced-by-count":29,"title":["Intestinal transport of bis(12)\u2010hupyridone in Caco\u20102 cells and its improved permeability by the surfactant Brij\u201035"],"prefix":"10.1002","volume":"32","author":[{"given":"Hua","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue Qing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanny C. 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