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Preclinical characterization of intestinal absorption and metabolism of promising anti-Alzheimer's dimer bis(7)-tacrine
Zhang L.; Yu H.; Li W.M.; Cheung M.C.; Pang Y.P.; Gu Z.M.; Chan K.; Wang Y.T.; Zuo Z.; Han Y.F.
2008
Source PublicationInternational Journal of Pharmaceutics
Volume357Issue:2018-01-02Pages:85
Abstract

The present study aims to investigate the preclinical intestinal absorption of bis(7)-tacrine (B7T) using different absorption models. In addition, potential intestinal and liver first-pass metabolism was evaluated by in vitro incubation of B7T with rat intestine and liver microsome. Results showed that the permeability of B7T across artificial membrane was pH dependent with rapid diffusion achieved at both pH 6.8 and 7.4. However, the absorptive permeability of B7T in Caco-2 cell model was substantially lower than that in the artificial membrane accompanied with over 56% of B7T being trapped within Caco-2 cells. In the rat in situ intestinal perfusion model, B7T was subject to an extensive intestinal extraction (>90%) with extremely low concentration of B7T detected in mesenteric blood, which was further found to be associated with the high tissue binding (99.9%) of B7T. In vitro incubation of B7T with rat liver and intestinal microsomes revealed that hydroxylation of B7T might mainly occur in rat liver rather than intestine. In conclusion, B7T is expected to have a low oral bioavailability in vivo, which may be due to its poor intestinal permeability, significant tissue binding and hepatic hydroxylation metabolism. © 2008.

KeywordBis(7)-tacrine Intestinal Absorption Metabolism
DOI10.1016/j.ijpharm.2008.01.037
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000256537300012
The Source to ArticleScopus
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, SAR, Hong Kong
2.Institute of Chinese Medical Sciences, University of Macau, Macau, China
3.Computer-Aided Molecular Design Laboratory, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, United States
4.XenoBiotic Laboratories, Inc., Plainsboro, NJ, United States
5.School of Applied Sciences, University of Wolverhampton, United Kingdom
6.School of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, Hong Kong
7.Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR, Hong Kong
Recommended Citation
GB/T 7714
Zhang L.,Yu H.,Li W.M.,et al. Preclinical characterization of intestinal absorption and metabolism of promising anti-Alzheimer's dimer bis(7)-tacrine[J]. International Journal of Pharmaceutics,2008,357(2018-01-02):85.
APA Zhang L..,Yu H..,Li W.M..,Cheung M.C..,Pang Y.P..,...&Han Y.F..(2008).Preclinical characterization of intestinal absorption and metabolism of promising anti-Alzheimer's dimer bis(7)-tacrine.International Journal of Pharmaceutics,357(2018-01-02),85.
MLA Zhang L.,et al."Preclinical characterization of intestinal absorption and metabolism of promising anti-Alzheimer's dimer bis(7)-tacrine".International Journal of Pharmaceutics 357.2018-01-02(2008):85.
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