title: Toxicokinetics and lack of uterotropic effect of orally administered S-equol.
abstract: S-equol is a natural product that is produced by the microbial biotransformation of daidzein, an isoflavone found in soy. Evidence suggests that the health benefits of soy may be related to one's ability to produce S-equol, thus S-equol is being developed for the treatment of vasomotor symptoms in postmenopausal women. The toxicokinetics of S-equol were evaluated in Sprague-Dawley rats and cynomolgus monkeys; S-equol was rapidly absorbed with C(max) occurring between 0.5 h and 1.0 h in the rat and 3h in the monkey. AUC was linear over the doses tested with no differences between male and female animals. Conjugated S-equol was the major metabolite in plasma with less than 1% present as the unconjugated form. S-equol showed a weak induction of liver cytochrome P450s in vivo, and did not significantly inhibit the major human cytochrome P450s in vitro. S-equol was highly protein bound (>95%) in rat, monkey and man in a concentration-independent manner. Orally administered S-equol did not significantly change uterine weight or morphology in either the rat or monkey even at the highest doses tested. These studies show that S-equol has pharmacokinetic parameters suitable for drug development with a low potential for uterotropic effects.
authors.affiliation: Ausio Pharmaceuticals, LLC, Cincinnati, Ohio 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: Jeffrey B
authors.initials: JB
authors.lastname: Plomley
authors.forename: Richard L
authors.initials: RL
authors.lastname: Jackson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D060754:Equol / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects*
chemical_list: D001798:Blood Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D060754:Equol; D003577:Cytochrome P-450 Enzyme System