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Lijuan Zhou1, Min Li1, Huihong Li1
1Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
沃里科纳 (VCZ) 对侵入性真菌感染的剂量是复杂的,因为变化. 使用年龄,体重,CYP2C19表型和CRP的新配方可以预测理想的维持剂量以获得更好的患者结果.
科学领域:
- 药物遗传学 药物遗传学
- 临床药理学 临床药理学
- 传染性疾病 传染性疾病
背景情况:
- 在侵袭性真菌感染 (IFI) 中,沃里康纳 (VCZ) 的血清最低度 (Cmin) 是高度可变的,影响治疗的有效性和安全性.
- 达到目标VCZ Cmin水平 (0.55.0 mg/L) 是至关重要的,但由于患者反应不可预测,具有挑战性.
- 影响VCZ药理动学的因素需要进一步阐明,以优化剂量策略.
研究的目的:
- 在IFI患者中确定影响伏利康纳Cmin和维持剂量的关键因素.
- 开发一个预测模型来确定最佳的沃里康纳维护剂量.
- 为了增强当前用于沃里康纳治疗的剂量指南.
主要方法:
- 一个随机的,前性的观察单中心研究,涉及306名成年IFI患者.
- 患者被分为非基因导向 (不考虑CYP2C19表型) 和基因导向 (考虑CYP2C19表型) 组.
- 使用回归分析开发了VCZ维持剂量的预测公式.
主要成果:
- CYP2C19遗传多态性显著影响VCZ加载和维持剂量选择.
- CYP2C19表型,C-反应蛋白 (CRP) 和平均每日剂量/体重影响了VCZ Cmin.
- 导出了一个预测公式:维持剂量 (毫克) = 282.774 - 0.735×年龄 + 2.946×体重 - 19.402×CYP2C19表型 - 0.316×CRP (p < 0.001).
结论:
- 开发的配方提供了一种可行的方法来预测沃里科纳的维持剂量.
- 这种模型可以补充现有的指导方针,特别是对于具有波动性炎症标记的IFI患者.
- 通过药物遗传学和临床因素的整合,优化伏利可纳的剂量可以改善治疗结果.
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