吸收,新陈代谢和分泌的
Jiyuan Ma1, Oscar L Laskin1, Ad F Roffel2
1PTC Therapeutics, United States.
Drug metabolism and disposition: the biological fate of chemicals
|October 18, 2023
概括
这项研究跟踪了使用放射标记在人类中使用emvododstat的新陈代谢和分泌. 一个新的剂量策略揭示了关键的代谢途径和排泄途径接近稳定状态药物水平.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物代谢和药理动力学
- 生物化学 生物化学
背景情况:
- 恩沃多斯塔特是一种强大的二基酸脱酶抑制剂.
- 它正在为COVID-19和急性髓性白血病进行临床研究.
- 人类的新陈代谢和恩沃多斯塔特的药理动力学是时间依赖的.
研究的目的:
- 为了评估emvododstat的新陈代谢和分泌,接近稳定状态.
- 使用重复剂量研究设计来描述emvododstat的药理动力学特征.
- 为了识别主要的循环和分泌代谢物.
主要方法:
- 一种微标志物和高放射性剂量的C-emvododstat的组合.
- 七名健康的男性受试者每天接受口服剂量,持续7天.
- 在血,全血,尿液和便中的放射性被量化.
主要成果:
- 剂后6小时,血和全血中的放射性达到峰值.
- 240小时后,尿液中的平均累积恢复率为6.0%,便中的平均累积恢复率为19.9%.
- 恩沃多斯塔特,M443和O-脱甲基恩沃多斯塔特葡萄糖化物是主要的循环成分;M474和O-脱甲基恩沃多斯塔特分别是主要的尿和便代谢物.
结论:
- 这项研究提供了Emvododstat在接近稳定状态时的全面吸收,新陈代谢和分泌数据.
- 一个重复剂量微型追踪器,其次是高剂量策略,有效地解决了缓慢新陈代谢和排泄的挑战.
- 这种方法可以在治疗相关剂量下对脂友性化合物进行表征.
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