马拉在老鼠和人类体内代谢清除
Gopinath Nallani1, Appavu Chandrasekaran2, Kelem Kassahun2
1FMC Corporation, 2929 Walnut St, Philadelphia, PA 19104, USA.
在老鼠和人类肝脏显微体中研究了马拉清除. 马拉单碳酸 (MMCA) 是主要代谢物,与幼鼠相比,成年老鼠的形成率更高.
科学领域:
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
- 代谢过程中的代谢.
背景情况:
- 马拉是一种有机酸盐杀虫剂.
- 了解马拉代谢对于风险评估至关重要.
研究的目的:
- 在成年和幼年老鼠和人类肝脏显微体中确定马拉的体内清除率.
- 为了将体外数据与老鼠体内药理动力学相关联.
- 为了帮助开发一种基于生理学的药理动力学 (PBPK) 模型.
主要方法:
- 在实验室内,使用成年和幼年老鼠和人类的肝脏显微体进行内在清除测定.
- 在静脉注射 (IV) 后,成年大鼠的药理动力学 (PK) 研究. 和口服的管理.
- 马拉及其代谢物,马拉单碳酸 (MMCA) 和马拉的量化.
主要成果:
- 通过MMCA形成的马拉的代谢清除发生在成人和青少年人类肝脏显微体中的速度相似.
- 鼠肝显微体显示,成年人与青少年的MMCA形成率高出10倍.
- 马拉在体内迅速被清除,MMCA被确定为主要代谢物.
结论:
- 观察到马拉代谢的年龄和物种差异,特别是在大鼠中.
- MMCA是主要的代谢物,马洛克森的形成很小.
- 生成的动力学数据对PBPK模型开发的马拉有价值.
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