西蒙特雷尔维尔/里托纳维尔的药物相互作用:一个开放标签,固定的序列,两期临床试验
Pan-Pan Ye1, Bu-Fan Yao2, Yang Yang3
1Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.
概括
辛诺特雷尔维尔/里托纳维尔可以安全地与CYP3A/P-gp抑制剂联合使用. 然而,避免与强大的CYP3A/P-gp诱导剂 (如利芬素) 联合使用,以防止暴露不足和不良事件.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物新陈代谢 药物新陈代谢
- 临床药理学 临床药理学
背景情况:
- 作为SARS-CoV-2蛋白酶抑制剂的simnotrelvir与里托纳维尔 (simnotrelvir/ritonavir) 配制.
- 这两种药物都是细胞染色体P450 3A (CYP3A) 和P-糖蛋白 (P-gp) 的基质和抑制剂,表明可能存在药物相互作用 (DDI).
- 了解这些DDI对于simnotrelvir/ritonavir的安全有效使用至关重要.
研究的目的:
- 为了研究simnotrelvir/ritonavir的药物相互作用潜力.
- 评估CYP3A和P-gp抑制剂和诱导剂对simnotrelvir药理动学的影响.
- 评估simnotrelvir/ritonavir对CYP3A基质米达佐拉姆药理学的影响.
主要方法:
- 在健康的中国成年人中进行了一项开放式,固定序列的I期临床试验.
- 三个队列评估了simnotrelvir/ritonavir与伊特拉科纳 (CYP3A/P-gp抑制剂),里芬素 (CYP3A/P-gp诱导剂) 和米达佐拉姆 (CYP3A基质) 的同时使用.
- 测量了药理动力学参数,包括AUC0-t.
主要成果:
- 与伊特拉科纳的同时使用,simnotrelvir AUC0-t增加了25%.
- 利芬素显著降低了simnotrelvir AUC0-t 81.5%,与增加的不良事件相关,包括肝毒性.
- 西姆诺特雷尔维尔/里托纳维尔增加了米达佐拉姆AUC0-t的16.69倍,表明显著的CYP3A抑制.
结论:
- 辛诺特雷尔维尔/里托纳维尔可以安全地与CYP3A/P-gp抑制剂联合使用.
- 应避免与强的CYP3A/P-gp诱导剂,如利芬素的同时使用,以防止治疗失败和毒性.
- 辛诺特里尔维尔/里托纳维尔显著抑制CYP3A,增加暴露于联合使用的CYP3A基质,如米达佐拉姆.
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