Pharmacokinetics and safety profile of single-dose administration of an estrogen receptor β-selective phytoestrogenic (phytoSERM) formulation in perimenopausal and postmenopausal women

Abstract

Objective: Selected estrogen receptor β-selective phytoestrogen (phytoSERM), a preparation of genistein, daidzein, and S-equol, has an 83-fold selective affinity for estrogen receptor (ER) β, and may promote neuronal survival and estrogenic mechanisms in the brain without exerting feminizing activity in the periphery. The aim of this study was to assess the safety, tolerability, and single-dose pharmacokinetics of the phytoSERM formulation in perimenopausal and postmenopausal women.

Methods: Eighteen women aged 45 to 60 years from a 12-week clinical trial evaluating cognitive performance and vasomotor symptoms were randomly assigned to placebo, 50 mg, or 100 mg phytoSERM treatment groups. Plasma levels of the three parent phytoestrogens and their metabolites were measured before and at 2, 4, 6, 8, and 24 hours after ingestion by isotope dilution high-performance liquid chromatography (HPLC) electrospray ionization tandem mass spectrometry.

Results: Plasma concentrations of genistein, daidzein, and S-equol peaked at 9, 6, and 4 hours, respectively, for the 50-mg dose, and at 6, 6, and 5 hours, respectively, for the 100-mg dose. The maximum concentration (Cmax) and area under the curve (AUC) for the three parent compounds were greater in the 100-mg dose group, indicating a dose-dependent change in concentration with the phytoSERM treatment. No adverse events were elicited.

Conclusions: A single-dose oral administration of the phytoSERM formulation was well-tolerated and did not elicit any adverse events. It was rapidly absorbed, reached high plasma concentrations, and showed a linear dose-concentration response in its pharmacokinetics. These findings are consistent with previously reported parameters for each parent compound (Clinicaltrials.gov NCT01723917).

Conflict of interest statement

Conflicts of interest: None reported.

Figures

Figure 1

(A) Plasma appearance and disappearance curves for daidzein, genistein, and equol in healthy peri- and post-menopausal women after single oral intake of 50 mg of phytoSERM. (B) Log/linear plots of plasma concentrations of daidzein, genistein, and equol after a single oral dose of 50 mg phytoSERM combination illustrating the charateristic linear slope seen in first-order elimination kinetics. Values are means ± SE, n=18

Figure 1

(A) Plasma appearance and disappearance curves for daidzein, genistein, and equol in healthy peri- and post-menopausal women after single oral intake of 50 mg of phytoSERM. (B) Log/linear plots of plasma concentrations of daidzein, genistein, and equol after a single oral dose of 50 mg phytoSERM combination illustrating the charateristic linear slope seen in first-order elimination kinetics. Values are means ± SE, n=18

Figure 2

(A) Plasma appearance and disappearance curves for daidzein, genistein, and equol in healthy peri- and post-menopausal women after single oral dose of 100 mg of phytoSERM. (B) Log/linear plots of plasma concentrations of daidzein, genistein, and equol after a single oral dose of 100 mg phytoSERM combination illustrating the charateristic linear slope seen in first-order elimination kinetics. Values are means ± SE, n=18

Figure 2

(A) Plasma appearance and disappearance curves for daidzein, genistein, and equol in healthy peri- and post-menopausal women after single oral dose of 100 mg of phytoSERM. (B) Log/linear plots of plasma concentrations of daidzein, genistein, and equol after a single oral dose of 100 mg phytoSERM combination illustrating the charateristic linear slope seen in first-order elimination kinetics. Values are means ± SE, n=18