来自比格尔犬的Ivermectin B1a的药理动力学研究
Yuyang Chen1, Xiaofang Huang2, Zizheng Guo2
1School of Pharmacy, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, Guangdong 511436, China.
Journal of chromatographic science
|December 22, 2023
概括
抗寄生虫药Ivermectin显示出抗病毒的潜力. 这项研究开发了一种经过验证的LC-MS/MS方法来分析 beagle 狗的 ivermectin 药理动力学,揭示了高脂肪餐和同时使用 P-gp 抑制剂的吸收增加.
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
- 抗病毒研究 抗病毒研究
背景情况:
- 伊弗麦丁是一种成熟的抗寄生虫剂,具有新兴的广泛抗病毒特性,包括对SARS-CoV-2的活性.
- 对ivermectin的药理动力学概况的有限理解需要进一步研究潜在的临床应用.
- 在血制备过程中,ivermectin在沉物中的显著分离突显了全血分析的必要性.
研究的目的:
- 开发和验证一种灵敏的液体染色仪-质谱仪 (LC-MS/MS) 方法,用于量化 beagle 狗全血中的 ivermectin.
- 在空腹和食 (高脂肪餐) 条件下研究小猎犬中ivermectin的口服药理动力学.
- 为了评估P-glycoprotein (P-gp) 抑制对ivermectin药理动力学暴露的影响.
主要方法:
- 根据FDA生物分析指南,开发和验证全血中ivermectin的LC-MS/MS测定方法.
- 在禁食和高脂肪饮食条件下,向 beagle 狗口服ivermectin.
- 与P-gp抑制剂黄素同时使用ivermectin,以评估药物相互作用对药理动学的影响.
主要成果:
- 经过验证的LC-MS/MS方法表现出卓越的特异性,准确性,精度和稳定性.
- 在禁食条件下,Ivermectin口服的结果是Cmax为104 ± 35μg·L−1和AUC0-∞为2,555 ± 941 h·μg·L−1.
- 一个高脂肪的食物增加了ivermectin的Cmax到147±35μg·L-1和AUC0-∞到4,198±1,279小时·μg·L-1,这代表暴露增加了约1.4倍.
- 与黄素 (P-gp抑制剂) 的同时使用进一步提高了Cmax至177 ± 57μg·L−1和AUC0-∞至4,213 ± 948 h·μg·L−1,与禁食相比增加了约1.6倍.
结论:
- 开发的LC-MS/MS方法适合在全血中进行ivermectin的药理动力学研究.
- 摄入食物,特别是高脂肪的食物,显著提高了ivermectin口服生物可用性.
- 通过与黄素同时使用的P-gp抑制,大大增加了对ivermectin的暴露,这表明P-gp在其处置中发挥了作用.
- 这些发现强调了通过与食物或P-gp调节器进行战略管理来优化ivermectin的临床疗效的潜力.
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