利纳普拉桑酸盐在老鼠中的吸收,分布,新陈代谢和分泌
Xinyue Zhang1, Donghui Liu1, Ming Lu2
1School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
Journal of pharmaceutical and biomedical analysis
|February 14, 2024
概括
利纳普拉桑酸盐是抑制酸的前药物,主要通过大鼠的便排出. 它在血中的主要代谢物是2,6-二甲基酸,CES2被确定为关键的水解酶.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物新陈代谢 药物新陈代谢
- 胃肠病学 胃肠病学
背景情况:
- 利纳普拉桑是一种具有快速分泌的竞争性酸阻塞剂.
- 利纳普拉桑酸盐是一种前药,旨在长时间抑制胃酸.
- 有限的数据存在于临床和非临床环境中linaprazan酸盐的代谢.
研究的目的:
- 在大鼠中研究林普拉桑酸盐的药理动力学,组织分布,质量平衡和代谢.
- 为了确定利纳普拉桑酸盐的主要分泌途径和代谢物.
- 阐明所涉及的代谢途径和关键酶.
主要方法:
- 对大鼠进行单次口服[14C]林普拉桑酸盐 (2.4 mg/kg) 的使用.
- 对血,尿液,便和胆汁进行与药物相关的物质和代谢物的分析.
- 药物动力学分析,包括AUC测量.
- 通过结构识别代谢物的代谢物.
主要成果:
- 利纳普拉桑酸盐主要通过便排出 (168小时内70.48%).
- 血AUC0-∞在雌性大鼠中比雄性大鼠高出两倍.
- 检测到13种代谢物; 2,6-二甲基酸 (M150) 是主要的血代谢物.
- 与药物相关的物质集中在胃,眼睛,肝脏和肠道中;主要在血中超过血细胞.
- 液解到林普拉桑,其次是氧化,脱和葡萄糖化,构成了主要的代谢途径.
结论:
- 利纳普拉桑酸盐在老鼠中表现出有利的质量平衡,主要通过便分泌.
- 在林普拉桑酸盐的药理动力学上观察到显著的性别差异.
- 鉴定出CES2是负责林普拉桑酸盐解至林普拉桑的主要酶.
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