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Intestinal Transport of Bis(12)-hupyridone in Caco-2 Cells andits Improved Permeability by the Surfactant Brij-35
Hua Yu1; Yue Qing Hu1; Fanny C. F. Ip1,2; Zhong Zuo4; Yi Fan Han3; Nancy Y. Ip1,2
2011-01-27
Source PublicationBiopharmaceutics & Drug Disposition
ISSN0142-2782
Volume32Issue:3Pages:140–150
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 mu M. However, only apical efflux was observed in the directional transport studies for B12H below 88 mM (P(app)(AP-to-BL): virtually zero; P(app)(BL-to-AP): 1.591 +/- 0.071 x 10(-5) cms(-1)). P-gp and mixed P-gp/MRP inhibitors significantly increased the absorptive transport (P(app)(AP-to-BL)) to 0.619 +/- 0.018 x 10(-5) and 0.608 +/- 0.025 x 10(-5) cms(-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 x 10(-5) cms(-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 similar to 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 mu M). Therefore, Brij-35 can be used as a potential enhancer to improve intestinal absorption of B12H for oral administration. 

KeywordBis(12)-hupyridone Absorption P-glycoprotein Multidrug Resistance-associated Protein Nonionic Surfactant
DOIhttp://www.doi.org/10.1002/bdd.745
Indexed BySCIE
Language英語English
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000289213700002
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Cited Times [WOS]:21   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorNancy Y. Ip
Affiliation1.Department of Biochemistry, Biotechnology Research Institute and Molecular Neuroscience Center, The Hong Kong University of Scienceand Technology, Clear Water Bay, Kowloon, Hong Kong SAR, PR China
2.State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon,Hong Kong SAR, PR China
3.Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University,Hung Hom, Kowloon, Hong Kong SAR, PR China
4.School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, PR China
Recommended Citation
GB/T 7714
Hua Yu,Yue Qing Hu,Fanny C. F. Ip,et al. Intestinal Transport of Bis(12)-hupyridone in Caco-2 Cells andits Improved Permeability by the Surfactant Brij-35[J]. Biopharmaceutics & Drug Disposition,2011,32(3):140–150.
APA Hua Yu,Yue Qing Hu,Fanny C. F. Ip,Zhong Zuo,Yi Fan Han,&Nancy Y. Ip.(2011).Intestinal Transport of Bis(12)-hupyridone in Caco-2 Cells andits Improved Permeability by the Surfactant Brij-35.Biopharmaceutics & Drug Disposition,32(3),140–150.
MLA Hua Yu,et al."Intestinal Transport of Bis(12)-hupyridone in Caco-2 Cells andits Improved Permeability by the Surfactant Brij-35".Biopharmaceutics & Drug Disposition 32.3(2011):140–150.
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