在中国人群中使用利康纳进行个性化治疗:炎症水平作为剂量优化的新标志物
Xu Hao1,2, Yuanyuan Li1,2, Ying Zhang1,2
1Department of Pharmacy, Peking University People's Hospital, Beijing, China.
British journal of clinical pharmacology
|September 28, 2023
概括
炎症显著影响伏利康纳 (VRC) 代谢,可能掩盖CYP2C19基因效应. 白蛋白和总胆红素水平也是VRC代谢的关键因素.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 遗传学 是一个遗传学.
- 临床医学 临床医学
背景情况:
- 沃里康纳 (VRC) 的代谢受遗传和非遗传因素的影响.
- 已知CYP2C19基因多态性会影响VRC的药理动力学.
- 炎症状态在VRC代谢中的作用需要进一步研究.
研究的目的:
- 研究与药理动力学相关的基因多态性,特别是CYP2C19,以及非遗传因素对中国人群中VRC代谢的影响.
- 探索遗传变异,非遗传因素和炎症状态对VRC代谢的综合影响.
- 阐明炎症对VRC代谢的影响背后的机制.
主要方法:
- 临床研究涉及120名患者,采用265个血液样本,测量VRC最低度和C-反应蛋白 (CRP) 水平.
- 多重回归分析以确定VRC度 (Cmin ss/D) 的预测因素.
- 在老鼠中进行非临床研究,以评估控制和炎症状态下的VRC平均停留时间 (MRT(0-t),通过IL-6/STAT3通路检查CYP2C19 (老鼠中的CYP2C6) 表达.
主要成果:
- 在没有或轻度炎症的患者中,CYP2C19基因型和白蛋白 (Alb) 水平预测了VRC度 (R2=0.12,P<.001).
- 在中度至重度炎症的患者中,CRP和总胆红素 (T-Bil) 水平形成了对VRC度的显著预测模型 (R2=0.19,P<.001).
- 在大鼠中,炎症显著增加了VRC MRT ((0-t),并与通过IL-6/STAT3途径降低CYP2C19 (CYP2C6) 的调节有关.
结论:
- 炎症状态可以掩盖CYP2C19多态对VRC代谢的影响,成为中度至重度炎症的一个更关键因素.
- 专蛋白和总胆红素水平是影响VRC代谢的重要非遗传因素,应该考虑.
- 了解这些综合影响对于优化VRC疗法至关重要,特别是在炎症条件下.
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