一项剂量检测研究指导使用维拉帕米尔作为结核病的辅助疗法
Chandrasekaran Padmapriyadarsini1, John D Szumowski2, Nabila Akbar1
1National Institute for Research in Tuberculosis, Chennai, India.
Clinical pharmacology and therapeutics
|November 20, 2023
概括
高剂量的维拉帕米尔可以安全地治疗结核病 (TB),当与里法相结合. 这种辅助疗法克服了药物代谢问题,可能缩短结核病治疗时间.
科学领域:
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
- 菌根细菌的研究研究.
背景情况:
- 结核菌 (Mtb) 耐药性,由排泄诱导驱动,阻碍了结核病 (TB) 治疗的缩短.
- 维拉帕米尔抑制了Mtb排泄,降低了对利法的耐受性和巨细胞中的Mtb生长.
- 维拉帕米尔作为辅助结核病治疗的潜力受到与里法平联合使用时快速代谢的限制.
研究的目的:
- 为了确定更高的维拉帕米尔剂量是否可以克服里法诱导的新陈代谢.
- 评估在接受 rifampin 的结核病患者中增加维拉帕米尔剂量的安全性和有效性.
主要方法:
- 一个剂量升级的临床试验,涉及肺结核患者.
- 持续释放 (SR) 维拉帕米尔的剂量升级与里法的管理.
- 维拉帕米尔及其代谢物 (诺维拉帕米尔) 和里法暴露的药理动力学分析.
主要成果:
- 每12小时服用360毫克SR维拉帕米尔的剂量达到与非里法治疗的患者相似的暴露.
- 里法的使用将维拉帕米尔的代谢转移到较少心脏活性的代谢产物和具有保留排泄抑制活性的酶体上.
- 维拉帕米尔的使用增加了50%的利法暴露,这表明了潜在的协同效应.
结论:
- 较高的维拉帕米尔剂量可以安全地与里法素一起使用,以抵消快速代谢.
- 这种方法增强了维拉帕米尔的治疗效益,因为它有利于活性代谢物和反体.
- 增加维拉帕米尔剂量代表了含有里法的结核病治疗方案的有前途的辅助疗法.
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