一项剂量确定研究,以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.
medRxiv : the preprint server for health sciences
|August 14, 2023
概括
维拉帕米尔可以抑制耐药的Mycobacterium结核病 (Mtb) 排泄. 高剂量的维拉帕米尔,结合利法,是安全有效的辅助结核病治疗,可能缩短治疗时间.
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
- 结核病研究 结核病研究
背景情况:
- 结核菌菌 (Mtb) 耐药性,由排泄诱导驱动,阻碍了缩短结核病治疗的努力.
- 维拉帕米尔抑制了Mtb排泄,降低了对利法的耐药性,并限制了巨细胞中的Mtb生长.
- 维拉帕米尔显示出作为缩短结核病 (TB) 治疗的辅助疗法的潜力,但其代谢在与里法联合使用时会显著改变.
研究的目的:
- 在一项临床试验中,评估与里法胺同时使用的较高维拉帕米尔剂量的安全性和有效性.
- 为了确定增加维拉帕米尔剂量是否可以克服里法诱导的加速新陈代谢.
- 评估维拉帕米尔给药对利法暴露和维拉帕米尔代谢物概况的影响.
主要方法:
- 进行了一项剂量升级的临床试验,以评估维拉帕米尔和里法的同时使用.
- 患者每12小时接受持续释放 (SR) 维拉帕米尔的升级剂量,并与里法一起服用.
- 分析了维拉帕米尔和里法的药理动力学参数,包括AUC (曲线下的面积),以及代谢物比率.
主要成果:
- 每12小时服用360毫克SR维拉帕米尔与里法的剂量,可达到与没有里法的标准剂量相似的维拉帕米尔暴露.
- 里法的使用有利于减少心脏活性的维拉帕米尔代谢物和反体,由AUC比率的增加表明.
- 维拉帕米尔的使用导致了显著增加的利法暴露.
- 较高的维拉帕米尔剂量在与里法的结合下安全耐受.
结论:
- 持续释放维拉帕米尔的较高剂量可以安全地与里法一起使用.
- 这种方法有效地抵消了利法诱导的维拉帕米尔代谢,维持了治疗性维拉帕米尔暴露.
- 维拉帕米尔,在较高的剂量下,可以安全地被整合到基于里法的疗法中,作为结核病的辅助疗法.
关键词:
在R-维拉帕米尔.药物耐受性 耐药性 药物耐受性流量 流量 流量 流量也没有诺维拉帕米尔.这就是为什么Rifampin是Rifampin.结核病是一种肺结核病.维拉帕米尔 (verapamil) 是一种非常有效的药物.更多相关视频
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