评估肠道CYP3A对药物相互作用的贡献与使用葡萄汁的延长释放塔克罗利木斯 (LCPT) 的药物相互作用
Adekunle Alabi1, Janice S Kerr2, Mita Shah3
1Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Clinical pharmacology in drug development
|January 19, 2026
概括
葡萄汁显著增加了移植患者使用延长释放Envarsus. tacrolimus的暴露. 这种相互作用在临床上是有意义的,尽管可能比立即释放的塔克罗利木斯更不严重.
科学领域:
- 药理学 药理学是指药理学的学科.
- 移植医学 移植医学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 葡萄汁 (GFJ) 抑制了肠道细胞染色体P450 3A (CYP3A),增加了对CYP3A基质的暴露,如塔克罗利斯.
- 延长释放塔克罗利斯 (LCPT) 在整个肠道中具有长时间的吸收.
- 之前没有评估过GFJ和LCPT之间的药物相互作用.
研究的目的:
- 评估GFJ对LCPT在成年移植接受者的药理学的影响.
- 为了确定LCPT的扩展吸收概况是否会改变其对GFJ介导药物相互作用的敏感性.
主要方法:
- 一项随机交叉研究,涉及11名接受稳定LCPT剂量的成年移植患者.
- 参与者在药理学访问期间接受了GFJ或水,米达佐拉姆作为阳性对照.
- 使用LC-MS/MS测量塔克罗利斯度,治疗之间有2-4周的洗期.
主要成果:
- 与对照组相比,高素AUC0-24在GFJ中高出28% (GMR=1.28).与对照组相比,高素AUC0-24在GFJ中高出28%.
- 与对照组相比,GFJ的塔克罗利斯Cmax高出73% (GMR = 1.73).与对照组相比,GFJ的塔克罗利斯Cmax高出73%.
- GFJ证明了与LCPT的临床意义上的相互作用,尽管可能比立即释放配方更明显.
结论:
- 葡萄汁在与延长释放塔克罗利斯 (LCPT) 联合使用时显著增加了塔克罗利斯的暴露.
- 与立即释放配方相比,LCPT的延长吸收概况可能会减轻药物相互作用的程度.
- 葡萄汁和延长释放塔克罗利斯之间的临床相关药物相互作用需要在脏移植接受者中考虑.
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