罗皮尼罗尔的新陈代谢是由几种犬类CYP酶调节的
Tuomas Tervahauta1, Päivi Uutela1, Mikko Koskinen1
1Orion Corporation, Orion Pharma, Espoo, Finland.
狗的罗皮尼罗尔代谢涉及多种CYP酶,而不仅仅是CYP1A2. 这一发现表明,犬类CYP1A2的变化不会显著影响罗宾的药理动力学.
科学领域:
- 兽医药理学 兽医药理学
- 药物新陈代谢 药物新陈代谢
- 生物化学 生物化学
背景情况:
- 人类医学中使用的罗皮尼罗尔可以通过多巴胺D2类受体在狗中诱导吐.
- 人类罗皮尼罗尔的新陈代谢主要由CYP1A2.2进行.
- 狗类CYP1A2是多态的,可能导致药物动力学变异.
研究的目的:
- 为了研究狗狗中罗皮尼罗尔的代谢清除.
- 为了确定负责狗中罗皮尼罗尔代谢的酶.
- 评估犬类CYP1A2多态性对罗皮尼罗尔清除的影响.
主要方法:
- 通过使用狗肝细胞和复合性犬类CYP异型来研究罗皮尼罗尔代谢.
- 采用LC质谱仪用于代谢物识别和量化.
主要成果:
- 罗皮尼罗尔在狗肝细胞中表现出中等稳定性 (Cl_int = 16.3 μL/分钟/百万细胞).
- 确定的主要代谢物包括7-基罗宾醇,其葡萄糖酸合物,以及despropyl ropinirole.
- 在CYP2B11,CYP2C21,CYP2D15,CYP1A2和CYP1A1中,代谢物形成率最高.
- 弗卢沃克萨明在多种犬类CYP异型中抑制了罗皮尼罗尔代谢,没有选择性.
结论:
- 多种犬类CYP异型对罗皮尼罗尔清除有贡献,与人类不同的是,CYP1A2占主导地位.
- 这种更广泛的代谢特征预计将减轻犬类CYP1A2遗传多态化对罗皮尼罗尔药理动学的影响.
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