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Masters Pharmacokinetics of flaxseed lignans in the rat

whisper

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Iraq Professor at Vet School
PHARMACOKINETICS OF FLAXSEED LIGNANS IN THE RAT
Valeriya Kotlyarova
ABSTRACT
Secoisolariciresinol 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.
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