人类第一次接触外源性单剂量口服estetrol早期绝经后妇女。

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维瑟M, Holinka CF,寇林格Bennink HJ

人类第一次接触外源性单剂量口服estetrol早期绝经后妇女。

更年期。2008;11增刊1:31-40。doi: 10.1080 / 13697130802056511。

PubMed ID

18464021 (在PubMed

]

文摘

目的:评估安全、耐受性、药物动力学和影响促性腺激素的单一剂量的升级estetrol (E (4))。方法:first-in-human研究E(4)进行早期绝经后妇女在健康。四个单剂量的0.1,1、10、100毫克E(4)分别为8个科目的学习小组进行评估,其中六个接受积极治疗和两个安慰剂治疗。安全性和耐受性是记录和一些药代动力学参数测定,是等离子体水平的促性腺激素促黄体激素(LH)和促卵泡激素(FSH)(药效学)。未来高剂量组登记后药代动力学评价和确认安全之前的组。结果:口服摄入后,血浆浓度的E(4)显示急剧增加,其次是急剧下降和增加二次剂量水平。Estetrol是分布式和吸收在第一次18 h后口服摄入。终端消除阶段开始24小时post-dose和半衰期(t((1/2)))范围10毫克组19至40 h(平均28.4小时,平均28.8 h)和100毫克组18到60 h(平均28.0小时,平均20 h),表明一剂半衰期的独立性。药代动力学参数也演示了一个高剂量反应关系,显示良好的一致性和低剂量组内差异。药效学数据显示剂量依赖性抑制血浆LH水平的E (4)。 A profound and sustained inhibition of FSH levels, lasting over 168 h, was observed in the 100 mg dose group (FSH was not measured in the other dose groups). Estetrol was well tolerated at all dose levels and no safety problems were encountered. CONCLUSIONS: Estetrol is orally absorbed and bioavailable with a strong dose-response relationship suggesting high oral bioavailability. Interindividual variations of plasma levels are low. The elimination half-life of 28 h suggests slow metabolism of E(4). The pharmacodynamic pattern complies with enterohepatic recirculation. Estetrol has a profound central inhibitory and dose-dependent effect on gonadotropins, confirming its biological potency.

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药物

Estetrol