title: Comparative pharmacokinetics of purified flaxseed and associated mammalian lignans in male Wistar rats.
abstract: Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed. Data on their bioavailability and hence pharmacokinetics (PK) are necessary to better understand their role in putative health benefits. In the present study, we conducted a comparative PK analysis of the principal lignan of flaxseed, secoisolariciresinol diglucoside (SDG), and its primary metabolites, secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL) in rats. Purified lignans were intravenously or orally administered to each male Wistar rat. SDG and its primary metabolites SECO, ED and EL were administered orally at doses of 40, 40, 10 and 10 mg/kg, respectively, and intravenously at doses of 20, 20, 5 and 1 mg/kg, respectively. Blood samples were collected at 0 (pre-dose), 5, 10, 15, 20, 30 and 45 min, and at 1, 2, 4, 6, 8, 12 and 24 h post-dosing, and serum samples were analysed. PK parameters and oral bioavailability of purified lignans were determined by non-compartmental methods. In general, administration of the flaxseed lignans SDG, SECO and ED demonstrated a high systemic clearance, a large volume of distribution and short half-lives, whereas administration of EL at the doses of 1 mg/kg (intravenously) and 10 mg/kg (orally administered) killed the rats within a few hours of dosing, precluding a PK analysis of this lignan. PK parameters of flaxseed lignans exhibited the following order: systemic clearance, SDG < SECO < ED; volume of distribution, SDG < SECO < ED; half-life, SDG < ED < SECO. The percentage of oral bioavailability was 0, 25 and < 1 % for SDG, SECO and ED, respectively.
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan,107 Wiggins Road,Saskatoon, Saskatchewan,Canada.
authors.forename: Jatinder Kaur
authors.initials: JK
authors.lastname: Mukker
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan,107 Wiggins Road,Saskatoon, Saskatchewan,Canada.
authors.forename: Ravi Shankar Prasad
authors.initials: RS
authors.lastname: Singh
authors.affiliation: Agriculture and Agri-Food Canada,Saskatoon, Saskatchewan,Canada.
authors.forename: Alister D
authors.initials: AD
authors.lastname: Muir
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan,107 Wiggins Road,Saskatoon, Saskatchewan,Canada.
authors.forename: Ed S
authors.initials: ES
authors.lastname: Krol
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan,107 Wiggins Road,Saskatoon, Saskatchewan,Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Alcorn
mesh_terms: D015107:4-Butyrolactone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002072:Butylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D019587:Dietary Supplements / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics; D019597:Flax / Q000737:chemistry*; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D006207:Half-Life; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007700:Kinetics; D017705:Lignans / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D048789:Phytoestrogens / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics; D011897:Random Allocation; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry*
chemical_list: D002072:Butylene Glycols; D004967:Estrogens; D005960:Glucosides; D017705:Lignans; D048789:Phytoestrogens; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; C060283:secoisolariciresinol; D015107:4-Butyrolactone; C090142:secoisolariciresinol diglucoside; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone
keywords: Serum protein binding