对Akuamma类化合物的综合性药理动力学和ADME评估
Abhishek Gour1, Simone M Creed2, Andrew P Riley2
1Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, United States.
概括
阿库阿玛树的化物显示出缓解疼痛的潜力,但需要进一步的研究来改善它们的吸收和生物可用性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 自然产品 化学 化学
- 药物新陈代谢和药理动力学
背景情况:
- 木 (Picralima nitida) 的种子传统上用于治疗发烧和疼痛.
- 阿库阿玛种子含有阿库阿米因,阿库阿米辛,阿库阿米林,皮克拉林和伪阿库阿米金等类化合物,它们以止痛,抗炎和改善情绪的作用而闻名.
研究的目的:
- 评估akuamma类化合物的体外和体内药理动力学.
- 开发和验证一种敏感的UPLC-MS/MS生物分析方法,用于量化这些化物.
- 为了提供关于阿库阿玛类化合物的吸收,分布,新陈代谢和分泌 (ADME) 特性的见解.
主要方法:
- 开发了一种敏感的UPLC-MS/MS生物分析方法,用于化物量化.
- 通过使用人类结直肠腺癌细胞单层进行体外透性评估.
- 在Sprague-Dawley大鼠体内评估药理动力学 (口服和静脉注射).
- 在大鼠肝脏显微体和血蛋白结合中确定了代谢稳定性.
主要成果:
- 在UPLC-MS/MS的方法是简单的,敏感的,和快速.
- 阿库阿玛类化合物表现出高的细胞透性.
- 在大鼠肝脏显微体中,水胺和水胺的半衰期很短 (13.5分钟和30.3分钟).
- 伪akuammigine显示了最高的血蛋白结合.
- 口服导致显著的全身暴露只有水氨酸,口服生物可用性低.
结论:
- 这项研究提供了第一个全面的ADME和akuamma类化合物的药理动力学数据.
- 这些发现凸显了在实现适当的全身暴露和口服生物利用性方面面临的挑战.
- 需要进一步的研究,以优化交付和增强这些化合物的治疗潜力,作为植物治疗剂来治疗疼痛.
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