QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 139/11/2037    most recent jn.109.110874v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Setchell, K. D. R. Articles by Ragland, K. PubMed PubMed Citation Articles by Setchell, K. D. R. Articles by Ragland, K.

---

Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

The Pharmacokinetics of S-(-)Equol Administered as SE5-OH Tablets to Healthy Postmenopausal Women^1,2

³ Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; ⁴ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH; and ⁵ Global Clinical Development, Otsuka Pharmaceutical Development & Commercialization, Rockville, MD 20850

The soy isoflavone metabolite, S-(-)equol, has selective affinity for estrogen receptor (ER)β 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.

^* To whom correspondence should be addressed. E-mail: kenneth.setchell{at}cchmc.org.

Manuscript received 1 June 2009. Initial review completed 30 June 2009. Revision accepted 29 August 2009.

Published online 23 September 2009.