Clinical characteristics and pharmacokinetics of purified soy isoflavones: Multiple-dose administration to men with prostate neoplasia
Clinical characteristics and pharmacokinetics of purified soy isoflavones: Multiple-dose administration to men with prostate neoplasia
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DOI：
10.1207/s15327914nc4802_5
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发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Zeisel, SH
中科院分区：
文献类型：
--
作者：
Fischer, L;Mahoney, C;Zeisel, SH
进行I期临床试验，以确定在患有前列腺肿瘤的男性中，口服给予三羟异黄酮（染料木黄酮和大豆黄酮，潜在的癌症化疗剂）的安全性、药代动力学参数和疗效。20名年龄在40岁及以上的前列腺B、C或D期腺癌患者用大豆异黄酮制剂的多次给药方案（递送大约300或600 mg/天的染料木黄酮和一半的大豆苷元）治疗84天。前列腺酮的递送剂量比前列腺癌患者通常服用的剂量高10倍以上。在患有前列腺癌的男性中，观察到慢性前列腺癌治疗的相对较小的副作用，包括一些雌激素效应（乳房变化，潮热频率增加）。治疗结束时，血清脱氢表雄酮下降31.7%（P = 0.0004）。除前列腺特异性抗原（PSA）值低于0.4 ng/ml的受试者外，受试者在试验前有PSA水平升高史。这种增加在试验期间持续，无论是在大豆异黄酮治疗期间还是在治疗停止后。平均而言，停止使用大豆异黄酮后，上升速度加快，但这种差异没有达到统计学意义。染料木黄酮和大豆苷元从血浆中迅速清除并经尿液排泄。长期给药的药代动力学数据与单剂量给药的研究，除了我们观察到大豆苷元的循环时间稍长。
A phase I clinical trial was conducted to determine the safety, pharmacokinetic parameters, and efficacy of orally administered isoflavones (genistein and daidzein, potential cancer chemotherapeutic agents) over a 3-mo period in men with prostate neoplasia. Twenty men, ages 40 and above, with stage B, C, or D adenocarcinoma of the prostate were treated with a multiple-dose regimen of a soy isoflavone formulation (delivering approximately 300 or 600 mg/day genistein and half this much daidzein)for 84 days. The delivered dose of isoflavones was more than 10-fold higher than that typically taken by prostate cancer patients. In men with prostate cancer, relatively minor side effects of chronic isoflavone treatment were observed including some estrogenic effects (breast changes, increased frequency of hot flashes). Serum dehydroepiandrosterone was decreased by 31.7% (P = 0.0004) at the end of treatment. Except for those subjects whose prostate-specific antigen (PSA) values were below 0.4 ng/ml, subjects had a history of increasing PSA levels prior to the trial. This increase continued during the trial both while on soy isoflavones and after treatment was discontinued. On average the rate of rise accelerated after soy isoflavones were discontinued, but that difference did not attain statistical significance. Genistein and daidzein were rapidly cleared from plasma and excreted in urine. Pharmacokinetic data for chronic dose administration were similar to single-dose administration for the isoflavones investigated except that we observed slightly longer circulation time for daidzein.