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Original Research Communication |
1 From the Department of Nutrition, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill (LTB, WL, MJS, TMB, CA, MGB, and SHZ); the Research Triangle Institute, Research Triangle Park, NC (ARJ, KJD, and BFT); and the Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD (JAC).
Background: Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers.
Objective: The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, daidzein, and glycitein in postmenopausal women.
Design: Twenty-four healthy postmenopausal women ingested a single dose of 1 of 2 purified (from soybeans) isoflavone preparations that delivered a genistein dose of 2, 4, 8, or 16 mg/kg body wt. These doses were higher than those previously administered to human females. Toxicity studies were performed 24 h and 3, 6, 14, and 30 d after isoflavone administration. Kinetic studies were performed during the first 24 h.
Results: We observed a 7% decrease in systolic and diastolic blood pressure and a 32% decrease in the neutrophil count 24 h after treatment with formulation A. Isolated episodes of nausea, pedal edema, and breast tenderness were judged to be possibly related to the study treatment. The terminal plasma half-lives for free genistein, daidzein, and glycitein averaged 3.8, 7.7, and 3.4 h, respectively. The terminal pseudo half-lives for total genistein and total daidzein in plasma averaged 10.1 and 10.8 h, respectively. The estimated bioavailabilities of both total genistein and total daidzein from each of the 2 formulations were not significantly different.
Conclusions: A single-dose administration of purified unconjugated isoflavones at amounts that exceed normal dietary intakes had minimal clinical toxicity in healthy postmenopausal women. The pharmacokinetic data suggest that chronic dosing at 12–24-h intervals would not lead to progressive accumulation of these isoflavones.
Key Words: Genistein • daidzein • glycitein • soy isoflavones • cancer • toxicity • pharmacokinetics • postmenopausal women
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