在猫中对KPT-335 (Verdinexor) 的药理动力学评估和生物可用性
Yuxin Yang1, Jinyan Meng1, Zeyu Wen1
1Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
该研究评估了KPT-335 (Verdinexor) 的药理动力学和猫的生物可用性. 药片的生物可用性高于囊,高剂量的非线性吸收,为临床剂量策略提供了信息.
科学领域:
- 药理学 药理学是指药理学的学科.
- 兽医医学 兽医医学 兽医医学
- 药物开发 药物开发
背景情况:
- KPT-335 (Verdinexor) 是一种选择性的核出口抑制剂,具有潜在的抗瘤和抗病毒应用.
- 了解其药理动力学特征和生物可用性对于治疗用途至关重要.
研究的目的:
- 为了确定KPT-335在猫的药理学参数和绝对生物可用性.
- 为了比较不同口服配方 (囊和药片) 和施用途径 (口服和静脉注射) 的生物利用性.
- 评估剂量和养条件对KPT-335药理动学的影响.
主要方法:
- 用超高性能液体染色学/并联质谱法对KPT-335在血中的药理动力学分析.
- 通过静脉注射和口服囊/片剂以各种剂量给予KPT-335.
- 使用WinNonlin 8.1进行非分区分析,以确定关键的药理学参数 (Cmax,AUC0-last,T1/2).
主要成果:
- 绝对生物利用率因配方和剂量而异,囊生物利用率从28.92%到44.66%不等.
- 药片的生物利用率高于囊,在禁食条件下达到75.92%,在体重1毫克/公斤的体重下达到1毫克/公斤.
- KPT-335表现出快速的吸收和排泄,在较高剂量时观察到非线性药理动力学,表明剂量依赖的吸收限制.
结论:
- KPT-335在猫身上显示出非线性药物动力学行为,特别是在较高剂量时.
- 药片配方与囊相比,具有更高的生物利用性.
- 这些发现对于在猫患者中确定KPT-335的适当临床剂量方案至关重要.
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