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提卡格勒勒增加了暴露于乳腺癌抗性蛋白质基质罗斯瓦斯塔丁的暴露
Minna Lehtisalo1,2,3, E Katriina Tarkiainen1,2,3, Mikko Neuvonen1,2
1Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.
提卡格勒勒在人类中显著增加了罗斯瓦斯塔丁水平,使其度增加了一倍以上. 这种药物相互作用,可能是由于蒂卡格勒勒抑制乳腺癌抗性蛋白 (BCRP),在同时使用高剂量罗斯瓦斯塔丁时需要谨慎.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物相互作用 药物相互作用
- 临床药理学 临床药理学
背景情况:
- 蒂卡格勒罗和罗斯瓦斯塔丁在动脉血事件后经常一起开处方.
- 据报道的狂犬病溶解病例表明,蒂卡格勒罗和罗斯瓦斯塔丁之间存在潜在的药物相互作用.
- 试验室研究表明,提卡格雷勒抑制了乳腺癌抵抗蛋白 (BCRP) 和参与罗斯瓦斯塔丁运输的有机阴离子载体聚 (OATP) 载体.
研究的目的:
- 为了研究与人同时服用蒂卡格勒勒对罗斯瓦斯塔丁的药理动力学影响.
- 量化蒂卡格勒对罗斯瓦斯塔丁血度,曲线下的面积 (AUC) 和半衰期的影响.
主要方法:
- 一项随机交叉研究,涉及9名健康志愿者.
- 参与者接受一次性剂量蒂卡格雷勒 (90毫克) 或安慰剂,然后在一个小时后接受罗斯瓦斯塔丁 (10毫克).
- 提卡格勒勒或安慰剂在初始剂量后的12,24和36小时内进行.
主要成果:
- 蒂卡格勒勒增加了血度-时间曲线 (AUC) 下的罗斯瓦斯塔丁面积和最大血度的2.6倍 (P < 0.003).
- 罗苏瓦斯塔丁的半衰期在与提卡格雷勒同时服用时从3.1小时延长到6.6小时 (P = 0.009).
- 罗斯瓦斯塔丁的干净度下降了11% (P = 0.032),而N-脱甲基罗斯瓦斯塔丁与罗斯瓦斯塔丁的比率保持不变.
结论:
- 提卡格勒勒在人类中显著提高了罗斯瓦斯塔丁度,可能是通过抑制肠道BCRP.
- 观察到的罗斯瓦斯塔丁水平的增加引发了对潜在的药物诱导肌肉毒性的担忧.
- 应避免同时使用蒂卡格勒罗与高剂量的罗斯瓦斯塔丁,以减轻安全风险.
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