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Permanent link (DOI): https://doi.org/10.7939/R3872H
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Absorption and Bioavailability of Glucosamine in the Rat Open Access
- Other title
- Type of item
- Degree grantor
University of Alberta
- Author or creator
Ibrahim, Alyaa, EA
- Supervisor and department
Jamali, Fakhreddin (Pharmaceutical Sciences)
- Examining committee member and department
El-Kadi, Ayman (Pharmaceutical Sciences)
Foster, Brian (Cellular and Molecular Medicine, University of Ottawa)
Jamali, Fakhreddin (Pharmaceutical Sciences)
Brocks, Dion (Pharmaceutical Sciences)
Doschak, Mike (Pharmaceutical Sciences)
Faculty of Pharmacy and Pharmaceutical Sciences
- Date accepted
- Graduation date
Doctor of Philosophy
- Degree level
Glucosamine (GlcN) is an amino monosaccharide that is widely used as a food supplement in the treatment of osteoarthritis (OA). In vitro and animal studies strongly support the therapeutic efficacy of the compound; however, clinical reports and meta-analysis are inconclusive. As compared to the concentration used to assess GlcN efficacy in vitro or in animal models, the maximum plasma concentration of 0.3-2 mg/ml typically seen following the recommended human oral dose of 1500 mg/day is sub-therapeutic. This is mainly due to the low oral bioavailability of GlcN.
The objectives of this thesis were to investigate the absorption kinetics of GlcN and to determine the different factors that may contribute in decreasing GlcN gut availability. We were able to improve a simple sensitive HPLC assay of GlcN in human and rat plasma with a lower limit of quantification (LLOQ) of 50 ng/mL. The method was further applied in our study.
In the current thesis we revealed that capacity-limited intestinal absorption was not behind the low oral bioavailability of GlcN, as both in vivo and in vitro results demonstrated linear absorption kinetics. GlcN intestinal absorption was found independent of glucose levels and food co-administration. The glucose transporter (GLUT2) is involved in GlcN intestinal absorption; however, passive diffusion may co-exist. Our in vitro studies confirmed that GlcN is absorbed throughout the intestinal tract with the highest permeability from the duodenum. An average of 14.52 6% could not be accounted for in the mass-balance determination after GlcN was incubated with the everted rat segments, indicating that part of the administered dose is either degraded or utilized by the intestinal tissue. Moreover, treating the rats with antibiotics prior to GlcN administration led to a pronounced increase in the compound bioavailability accompanied by a significant increase in the percent of the oral dose excreted unchanged in the rat feces (p < 0.05), from 0.11 ± 0.15% in the control rat to 11.18 ± 4.9% in the antibiotic treated rats. This points to a significant degradation by the intestinal flora that may at least in part explain the low oral bioavailability of GlcN.
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- Citation for previous publication
Ibrahim A & Jamali F (2010) Improved sensitive high performance liquid chromatography assay for glucosamine in human and rat biological samples with fluorescence detection. J Pharm Pharm Sci 13, 128-135Ibrahim A, Gilzad-Kohan MH, Aghazadeh-Habashi A & Jamali F (2012) Absorption and bioavailability of glucosamine in the rat. J Pharm Sci 101, 2574-2583.
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