大麻醇的生物可用性是非单调的,具有较长的终端消除半衰期:基于药理动力学建模的分析
1PMI R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
Cannabis and cannabinoid research
|April 16, 2024
概括
Cannabidiol (CBD) 具有很长的排泄半衰期,并且需要超过 70 天才能在口服剂量下达到稳定状态. 吸入输送可能通过绕过新陈代谢提供更一致的CBD暴露.
科学领域:
- 药理动力学 药理动力学
- 药物新陈代谢 药物新陈代谢
- 大麻素研究 研究 大麻素研究
背景情况:
- Cannabidiol (CBD) 用于口服和通过吸入用于各种疾病.
- 长期暴露CBD的动力学和生物可用性需要进一步描述.
研究的目的:
- 描述CBD的长期药理动力学 (PK) 概况.
- 为了评估CBD的非单调口服生物可用性.
- 为了比较CBD的口服和吸入输送方法.
主要方法:
- 利用了口服 (Epidiolex®) 和吸入研究中的人类CBD血度-时间数据.
- 应用了一个具有韦布尔吸收动力学的四个隔间PK模型.
- 使用Cedergreen-Ritz-Streibig模型来评估口服生物可用性.
主要成果:
- CBD具有广泛的组织分布,终端半衰期超过134小时.
- 口服CBD需要超过70天才能达到稳定状态的血度,每天服用一次.
- 在禁食状态下,口服生物可用性是非单调的 (反转的U形),受食物和肝功能障碍的影响.
- 吸入输送绕过了第一通代谢,潜在地提供了高效和一致的暴露.
结论:
- 由于非单调的生物可用性,CBD的药理动力学因剂量而异.
- 与口服途径相比,吸入可能会降低CBD暴露的变化.
- 延迟达到稳定状态和延长半衰期需要考虑长期的CBD剂量策略.
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