在SD大鼠中使用经过验证的UPLC和LC-MS方法进行了finerenone的药理动力,组织分布,透性,蛋白质结合和稳定性研究
Shivam Rathaur1, Parag Varshney2, Debalina Maity2
1Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India.
概括
这项研究开发了一种生物分析方法来分析Finerenone (FNR) 药理动力学和大鼠组织分布. FNR表现出良好的溶解性,稳定性和高透性,支持其在糖尿病病中的临床应用.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 药物代谢和药理动力学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 费内伦 (FNR) 是一种用于糖尿病病的新型非类固醇矿物质皮质类受体对抗剂.
- 经过验证的生物分析方法对于了解FNR在生物体中的行为至关重要.
研究的目的:
- 开发和验证一种敏感的LC-MS/MS生物分析方法,用于大鼠血中的FNR.
- 确定FNR在斯普拉格-道利 (SD) 鼠中的药理动力学 (PK) 和组织分布 (TD).
- 评估FNR的体外特性,包括溶解性,稳定性,透性和与血蛋白结合.
主要方法:
- 液体染色学与双重质谱学 (LC-MS/MS) 结合用于生物分析.
- 在口服和静脉注射后的体内PK和TD研究.
- 在体外评估:溶解性,模拟的肠/胃液稳定性,血稳定性,微体稳定性,血蛋白结合 (PPB),血分离,PAMPA和现场SPIP.
主要成果:
- 与胃液 (FaSSGF) 相比,FNR在肠液 (FaSSIF) 中具有更高的溶解度和稳定性.
- FNR表现出良好的血稳定性 (91.98%) 和大鼠肝脏显微体 (90.30%) 的显著代谢.
- 观察到高血蛋白结合 (94.11-96.97%),快速的血平衡,以及高的被动透性 (PAMPA,SPIP). 绝对口服生物利用率为49.17%.
结论:
- 开发的LC-MS/MS方法适用于FNR生物分析.
- FNR具有有利的物理化学和药理动力学特性,包括良好的吸收和分布.
- 这些发现支持Finerenone的临床前和临床应用,用于治疗与糖尿病相关的慢性病.
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