The pharmacokinetics of S-(-)equol administered as SE5-OH tablets to healthy postmenopausal women.
The soy isoflavone metabolite, S-(-)equol, has selective affinity for estrogen receptor (ER)beta and also antagonizes in vivo the action of dihydrotestosterone. It is therefore of interest as a potential new therapeutic agent in hormone-dependent conditions and is under development as a nutraceutical. Our objective in this study was to define the pharmacokinetics of natural S-(-)equol after administration of SE5-OH, a newly developed S-(-)equol supplement made by incubation of the equol-producing bacterium Lactococcus garvieae with soy germ isoflavones. In a single-center, open-label, randomized, 2-period crossover design study, the pharmacokinetics of S-(-)equol administered as single-bolus oral doses of 10 and 30 mg in the form of SE5-OH tablets was determined in 12 healthy postmenopausal women. S-(-)equol was measured in plasma and urine collected at timed intervals over a 48-h period postdosing using tandem MS. Equol-producer status was also determined after a soymilk challenge conducted after the pharmacokinetic sampling was complete. S-(-)equol was rapidly absorbed after oral administration and attained high plasma concentrations, with a plasma elimination half-life of 8 h. The maximum plasma concentration/dose, area under the plasma concentration-time curve from time 0 to infinity/dose, and the fraction of dose excreted in urine (%f(e,u)) were similar for the 2 doses, indicating a dose-proportional response in total S-(-)equol pharmacokinetics. The systemic bioavailability of S-(-)equol was very high, as the %f(e,u) was 82% for both doses, which is greater than published data for the soy isoflavones daidzein and genistein. Three participants were determined to be equol-producers, representing a 25% frequency, and equol-producer status had no effect on natural S-(-)equol pharmacokinetics.
Setchell
Kenneth D R
KD
Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. kenneth.setchell@cchmc.org
Zhao
Xueheng
X
Shoaf
Susan E
SE
Ragland
Karen
K
D000284:Administration, Oral; D000368:Aged; D015992:Body Mass Index; D018592:Cross-Over Studies; D060754:Equol; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007297:Inpatients; D007529:Isoflavones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008875:Middle Aged; D017698:Postmenopause; D012016:Reference Values; D013607:Tablets
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D007529:Isoflavones; D013607:Tablets; D004958:Estradiol; D060754:Equol; D005640:Follicle Stimulating Hormone