title: Elucidation of the metabolic pathway of S-equol in rat, monkey and man.
abstract: S-equol is a selective estrogen receptor β (ERβ) agonist which is produced in certain individuals after ingestion of its precursor daidzein, an isoflavone present in soy. S-equol is thought to provide certain health benefits, including reduced menopausal symptoms. The metabolic profile of S-equol was determined in vivo in Sprague-Dawley rats and cynomolgus monkeys, and in vitro using hepatocytes from rat, monkey, and human. High resolution MS fragmentation patterns indicated that the major metabolite of S-equol in rat plasma and urine was the 4'-glucuronide conjugate, with lesser amounts of unconjugated S-equol, the 7-sulfate conjugate, and the 4'-glucuronide-7-sulfate diconjugate. Monkeys also showed extensive metabolism, with the major species in plasma being the 4'-glucuronide and the 7-sulfate-4'-glucuronide diconjugate; urine contained primarily the 4'-glucuronide, as seen in the rat. In vitro metabolism by hepatocytes was extensive and similar in all species, with fragmentation patterns also indicating that the 4'-glucuronide was the major metabolite. No oxidative metabolites of [(14)C] S-equol were detected in either in vivo or in vitro studies. These findings show that glucuronidation is the primary pathway for the metabolism of S-equol in rat, monkey and man, and that all metabolic routes of S-equol observed in vitro were also observed in vivo.
authors.affiliation: Ausio Pharmaceuticals, LLC, Cincinnati, OH 45212, USA. rick@ausiopharma.com
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Schwen
authors.forename: Linh
authors.initials: L
authors.lastname: Nguyen
authors.forename: Richard L
authors.initials: RL
authors.lastname: Jackson
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D015925:Cryopreservation; D060754:Equol / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D020719:Glucuronides / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D013058:Mass Spectrometry; D048789:Phytoestrogens / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013431:Sulfates / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D020719:Glucuronides; D048789:Phytoestrogens; D013431:Sulfates; D060754:Equol