Study on the Pharmacokinetics of Synthetic Genistein after Multiple Oral Intake in Post-menopausal Women

Abstract

Genistein (CAS 446-72-0), an isoflavone and phytoestrogen predominantly found in soy, is considered a promising natural bioactive to prevent post-menopausal bone loss. geniVida (previously Bonistein), a novel product containing of min. 98.5% synthetic genistein aglycone, was investigated in 12 healthy post-menopausal women to assess the safety and tolerability as well as to obtain pharmacokinetic data after 7 days of repeated intakes. 24 h pharmacokinetic profiles were determined after the first oral dose and after 7 days repeated intakes of 30 mg of the test formulation. Plasma genistein (aglycone) and its conjugates were determined by a standardised LC/MS analytical method using D4-genistein as the internal standard. The plasma-concentration time profiles for conjugated genistein showed a fast, monophasic one-peak course until T(max) (5.9 h (first dose), 5.3 h (steady state (SS)); C(max) (456.8 ng/ml (first dose), 498.5 ng/ ml (SS)). Elimination half-lives (t1/2) were calculated to be 10.8 h (first dose) and 8.2 h (SS), respectively. Determination of AUC(0-inf.)) (first dose) was good with a low percentage of extrapolation (3949.1 h ng/ ml). AUC(0-24h) at SS was 5923.3 h ng/ml. Steady state was reached after 4 to 5 days and no relevant accumulation occurred (R = 1.02). The test formulation was safe and very well tolerated.