在人体中,重复服用里法的多种影响对甲的度
Jonny Kinzi1, Markus Grube2, Karin Brecht1
1Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Clinical and translational science
|September 14, 2023
概括
利法增加了血清中的甲 (CP) 水平,这表明除了有机阴离子转运聚 (OATP) 抑制之外的相互作用. 这项研究量化了接受里法的参与者的CP和血红素.
科学领域:
- 发现生物标志物的发现.
- 药物代谢和运输 药物代谢和运输
- 血红细胞生物合成
背景情况:
- 内源基质,如甲 (CPs) 是新兴的生物标志物,特别是有机离子载体聚 (OATP) 1B 载体相互作用.
- 利法是一种OATP抑制剂,也与孕前X受体 (PXR) 相互作用,诱导参与血红蛋白生物合成的基因.
研究的目的:
- 为了研究多剂量里法胺对血清CP和血红蛋白水平的影响.
- 探索利法与超越OATP抑制的CP水平的潜在相互作用.
主要方法:
- 在一项涉及12名健康参与者的试验中储存的临床血清样本中量化CP异构体 (CPI,CPIII) 和血红素.
- 在基线,在里法的服用期间和停止治疗14小时后分析样本.
主要成果:
- 在长期储存后,血清中CP水平是可量化的.
- 在利法的峰值度下观察到更高的CP水平,并在停止治疗后14小时内持续存在.
- 没有检测到对血清血红水平的显著影响.
- 在基线CP异构体和14小时后rifampin之间发现了相关性.
结论:
- 多剂量利法胺显著影响血清CP水平.
- 证据表明,利法与CP水平的相互作用超出了肝脏OATP抑制的范围,可能涉及PXR介导对血红蛋白生物合成的影响.
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