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dc.contributor.advisorAlcorn, Janeen_US
dc.creatorKotlyarova, Valeriyaen_US
dc.date.accessioned2013-01-03T22:27:12Z
dc.date.available2013-01-03T22:27:12Z
dc.date.created2010-09en_US
dc.date.issued2011-10-04en_US
dc.date.submittedSeptember 2010en_US
dc.identifier.urihttp://hdl.handle.net/10388/ETD-2010-09-126en_US
dc.description.abstractSecoisolariciresinol diglucoside (SDG) is the principal lignan of the flaxseed. In the human body it is metabolized to secoisolariciresinol (SECO) and then to enterodiol (ED) and enterolactone (EL). It has been shown that these compounds help to prevent the development of some hormone dependent diseases (breast, prostate cancers) and type II diabetes. Given numerous health benefits, evaluation of lignan pharmacokinetics is critical to understanding their pharmacology. This research aimed to assess SECO pharmacokinetic parameters in the rat. The first objective was to isolate pure SDG and SECO sufficient for a pharmacokinetic study. SDG (≥95% purity) was obtained from SDG (40% purity) by preparative HPLC. SECO (≥95% purity) was produced from SDG by acid hydrolysis. The second objective was to develop and validate an HPLC method with fluorescence detection suitable for pharmacokinetic applications. The method is specific for SECO, ED, and EL quantification in rat serum. Separation is achieved with a C18 reversed-phase column under gradient mobile phase conditions, consisting of water and acetonitrile buffered with 0.1% formic acid. Analytes are extracted with diethyl ether and 7-hydroxycoumarin serves as an internal standard. Calibration curves are linear from 0.01 to 10 µg/mL for SECO/ED and 0.05-10 µg/mL for EL. Accuracy and precision are within FDA specified limits. The third objective was to assess the pharmacokinetics of SECO after a single intravenous (20mg/kg) and oral bolus (40 mg/kg) administration in rat. SECO pharmacokinetic parameters were assessed based on a 12-hour study in Wistar male rats (n=12). The results were reported as mean ± SD: systemic clearance 3.1±1.0 L/h, volume of distribution 17.7±8.3 L, half-life 4.7±3.6 h, and oral bioavailability 26 %. SECO undergoes enterohepatic recirculation and exhibits two-compartment model characteristics with large volume of distribution and low oral bioavailability. An additional 48-hour study indicated that SECO is present in systemic circulation at least for 21 hours after dosing. ED was detected and quantified in the 8-24 hours samples, while EL was detected in 15-36 hours samples after SECO administration. Additional pharmacokinetic studies with ED and EL are necessary to understand which lignan form may mediate the beneficial health effects.en_US
dc.language.isoengen_US
dc.subjectlignan pharmacokinetics, flaxseed, HPLCen_US
dc.titlePharmacokinetics of Flaxseed Lignans in the Raten_US
thesis.degree.departmentPharmacy and Nutritionen_US
thesis.degree.disciplinePharmacyen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMaster of Science (M.Sc.)en_US
dc.type.materialtexten_US
dc.type.genreThesisen_US
dc.contributor.committeeMemberDobson, Roy T.en_US
dc.contributor.committeeMemberOlkowski, Andrzej A.en_US
dc.contributor.committeeMemberMansell, Kerry D.en_US


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