在CKD患者中,维卡德罗斯塔特对阿尔多合成酶抑制的药理学
Isabella A Gashaw1, Katherine R Tuttle2,3, Manuel Monroy Kuhn4
1Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein.
European journal of endocrinology
|December 23, 2025
概括
维卡德罗斯塔特在慢性脏病患者中选择性地抑制了阿尔多素合成,而不会影响皮质醇水平. 这种选择性阿尔多激素抑制在第二阶段试验中得到证实,为进一步研究铺平了道路.
科学领域:
- 内分泌学 在内分泌学.
- 腎臟病學 (nephrology) 是一種醫學專業.
- 药理学 药理学是指药理学的学科.
背景情况:
- 阿尔多氨酸合成酶 (CYP11B2) 和皮质醇合成酶 (CYP11B1) 具有相同的结构,这引发了人们对CYP11B2抑制剂的非向效应的担忧.
- 专性慢性病 (CKD) 和2型糖尿病 (T2D) 与阿尔多激素失调有关.
- 选择性CYP11B2抑制是管理这些疾病的潜在治疗策略.
研究的目的:
- 为了评估vicadrostat的选择性,一个强大的阿尔多素合成酶抑制剂,抑制阿尔多素与影响皮质醇合成.
- 评估维卡德罗斯塔特对阿尔伯尿性CKD患者的皮质类固醇样本的影响,有或没有T2D.
主要方法:
- 一个随机,双盲,安慰剂控制的第二阶段试验 (NCT05182840) 涉及410名患有白性结核病的参与者.
- 参与者接受了empagliflozin或安慰剂,随后在14周内重新随机化为vicadrostat (3,10或20毫克) 或安慰剂.
- 血皮质类固醇 (阿尔多斯特,皮质醇,皮质,11-脱氧皮质,11-脱氧皮质醇) 使用液体染色学二联质谱法进行测量.
主要成果:
- 维卡德罗斯塔特表现出剂量依赖的血阿尔多激素抑制,在20毫克时最大降低约50%.
- 在维卡德罗斯塔特治疗时,前体皮质类固醇 (皮质,11-脱氧皮质,11-脱氧皮质醇) 的显著增加.
- 在vicadrostat剂量组中没有检测到血皮质醇水平的显著变化,这表明选择性.
结论:
- 维卡德罗斯塔特可以选择性地抑制阿尔多斯特,而不会影响白性CKD患者的皮质醇合成.
- 观察到的前体皮质类固醇的增加在治疗后正常化.
- 这些发现支持在CKD管理的第三阶段试验计划中探索vicadrostat.
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