解释为什么剂量校正区域在替代给药途径的曲线下可能比静脉注射剂量更大
Hirokazu Wakuda1,2, Yue Xiang1, Jasleen K Sodhi1,3
1Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, San Francisco, California, 94143-0912, USA.
The AAPS journal
|January 30, 2024
概括
超过1.0的生物利用率 (F),通过曲线下的系统度面积 (AUC) 计算,可能是准确的. 吸收率影响AUC,挑战传统的生物可用性计算,并可能高估药物暴露.
科学领域:
- 药理动力学 药理动力学
- 药物的新陈代谢和处置
- 生理学建模 生理学建模
背景情况:
- 基于曲线下的系统度面积 (AUC) 的传统生物可用性 (F) 计算假设F不能超过1.0.
- 从尿液数据计算的生物利用率与系统AUC数据之间的差异以前归因于测量不准确性.
- 既定的药理动力学原理表明,吸收率不会影响从口服剂量的系统性清除的确定.
研究的目的:
- 挑战生物可用性 (F) 计算的传统理解,特别是当F > 1.0.0.时.
- 为了证明AUC测量可能会因为吸收率的影响而高估生物可用性.
- 为了验证报告F>1.0和不同系统与尿液生物可用性预测的研究.
主要方法:
- 使用PubMed的35种药物的文献综述,报告的F>1.0使用PubMed.
- 从AUC和尿液分泌数据计算的生物利用率进行比较的研究分析.
- 应用Kirchhoff定律来重新评估控制生物可用性的药理学原理.
主要成果:
- 系统生物可用性 (F) 可能被高估,因为AUC包含吸收率特征,而不仅仅是消除.
- 为了使F (AUC) 准确地反映F (尿),从吸收部位的清除必须超过静脉注射后的清除.
- 报告F>1.0和更大的系统与尿液生物可用性预测的研究可能是科学有效的.
结论:
- 在某些情况下,生物可用性计算的普遍接受的概念可能需要修订.
- 吸收率显著影响AUC值,可能导致过度估计生物可用性.
- 这些发现不会改变目前的监管生物等价性测试指南或在剂量决定中使用AUC.
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