Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women
Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women
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DOI：
10.1093/ajcn/76.5.1126
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发表时间：
2002-11-01
影响因子：
7.1
通讯作者：
Zeisel, SH
中科院分区：
文献类型：
--
作者：
Bloedon, LT;Jeffcoat, AR;Zeisel, SH
背景：大豆异黄酮正被评估作为乳腺癌及其他癌症的化学预防剂。
目的：本研究目的是对绝经后女性服用含染料木黄酮、大豆苷元和黄豆黄素的纯化非结合型异黄酮制剂进行安全性和药代动力学研究。
设计：24名健康绝经后女性单次服用从大豆中纯化的两种异黄酮制剂中的一种，所给予的染料木黄酮剂量为2、4、8或16mg/kg体重。这些剂量高于以往给予女性的剂量。在异黄酮给药后24小时以及3、6、14和30天进行毒性研究。在最初24小时内进行动力学研究。
结果：我们观察到服用制剂A 24小时后收缩压和舒张压下降7%，中性粒细胞计数下降32%。孤立的恶心、足部水肿和乳房胀痛发作被判定可能与研究治疗有关。游离染料木黄酮、大豆苷元和黄豆黄素的血浆终末半衰期平均分别为3.8、7.7和3.4小时。血浆中总染料木黄酮和总大豆苷元的终末假半衰期平均分别为10.1和10.8小时。两种制剂中总染料木黄酮和总大豆苷元的估计生物利用度无显著差异。
结论：单次给予超过正常膳食摄入量的纯化非结合型异黄酮对健康绝经后女性的临床毒性极小。药代动力学数据表明，以12 - 24小时为间隔长期给药不会导致这些异黄酮的渐进性蓄积。
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.