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给药时间错误对药物动力学分析中的清除估计的影响
Katsukuni Fujimoto1,2, Kazuhiko Asari2, Kiyoshi Mihara1
1Musashino University, Tokyo, Japan.
Clinical and translational science
|December 17, 2025
概括
给药时间错误显著影响药物清除 (CL) 估计,这是一个关键的药物动力学参数. 较短的药物半衰期 (t1/2) 会导致更大的CL低估,这可能会影响维持剂量选择.
科学领域:
- 药理动力学 药理动力学
- 药物的新陈代谢和处置
- 计算药理学计算药理学
背景情况:
- 准确估计药物清除 (CL) 对于确定适当的药物剂量和预测药物暴露至关重要.
- 给药时间错误可能会导致药理动力学 (PK) 参数估计出现偏差.
- 了解时间错误对CL的影响对于强大的临床药理学至关重要.
研究的目的:
- 综合评估如何给药时间错误影响药物清除率 (CL) 的估计.
- 确定控制时间错误,药物半衰期 (t1/2) 和CL估计偏差之间的关系的一般原则.
- 为了评估CL的临床相关性,由于时间不准确导致的CL估计错误.
主要方法:
- 模拟了23种假设化合物,具有不同的CL,分布体积 (Vd) 和消除半衰期 (t1/2).
- 在最后一次剂量前一天,引入了4,8小时和12小时的注射时间错误.
- 通过使用三个口服药物进行了两部分分析,这些药物具有不同的PK配置文件,以评估强度.
主要成果:
- 对于2-26小时之间的t1/2化合物,特别是较短的t1/2值 (4-5小时),发生了显著的CL低估.
- 平均CL低估达到7.1%,17.7%和31.1%,分别为4小时,8小时和12小时的计时错误.
- 临床临床错误的大小主要取决于t1/2,较大的错误和较短的t1/2导致更大的偏差.
结论:
- 给药时间错误,特别是较大的错误 (例如,12小时),可能会导致CL估计中的临床相关偏差.
- 消除半衰期 (t1/2) 是影响CL低估程度的关键因素.
- 这些发现凸显了准确的药物给药时间对于可靠的药理动力学评估和剂量选择的重要性.
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