了解阿德福维尔的药理动力学作为载体表型化尾酒的组成部分
Qian Dong1, Chunli Chen2,3, Max Taubert2
1Department I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Gleueler Straße 24, Cologne, 50931, Germany. qdong2@smail.uni-koeln.de.
European journal of clinical pharmacology
|March 28, 2024
概括
阿德福维尔迪普西尔的使用情况
科学领域:
- 药理动力学和药物新陈代谢
- 脏输送器表型化 脏输送器表型化
- 种群药动力学建模 种群药动力学建模
背景情况:
- 在之前的研究中,Adefovir dipivoxil被用作测试药物来评估脏有机离子载体1 (OAT1).
- 在与其他药物联合使用时,阿德福维尔的全身暴露量大约增加了20%.
- 人口药理动力学 (popPK) 建模用于进一步分析阿德福维尔的药理动力学.
研究的目的:
- 详细介绍当作为尾酒成分使用时的阿德福维尔迪普西尔的药理动力学.
- 调查联合使用药物对阿德福维尔暴露的影响.
- 评估干净度 (CLR) 适用于评估OAT1活动的适用性.
主要方法:
- 重新分析了24名健康受试者的药理动力学数据.
- 应用一个单间模型,具有一级吸收和滞后时间.
- 共变量分析包括使用前向和后向清除的同时使用的药物.
主要成果:
- 一个带有非线性脏和线性非脏排泄的单间模型最好地描述了阿德福维尔的药理动力学.
- 在联合使用期间,明显的生物利用率更高 (73.6%vs.59.0%),吸收率更低 (2.29h-1vs5.18h-1).
- 在单一和联合服用期间之间没有观察到脏排泄的显著差异.
结论:
- 同时使用主要影响阿德福维尔迪皮西尔的吸收和/或前药转化,而不是脏排泄.
- 观察到的轻微药物相互作用归因于吸收的改变,阿德福维尔作为受害者.
- 对于脏消除的高Km值表明CLR是评估使用尾酒剂量的脏OAT1活性的可靠参数.
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