在人体肝脏中,阿雷卡坚果异种生物的体外水解
Vincenzo Paolillo1, Mahendran Jayakumar2, Colton Sheperd2
1Cyclotron Radiochemistry Facility, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Drug metabolism and pharmacokinetics
|December 12, 2024
概括
在人类肝脏中研究了阿雷卡坚果化物阿雷科林和瓜科林的新陈代谢. 阿雷科林的清除率很高,表明肝脏有显著的水解,与瓜科林不同.
科学领域:
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 尽管已知有毒性,但阿雷卡坚果 (AN) 的消费普遍存在.
- 在AN中的甲基类类化合物,如阿雷科林和瓜科林,具有精神活性和毒性作用.
- 人类对这些类化合物的新陈代谢仍然不完全理解.
研究的目的:
- 研究人类肝脏中阿雷科林和瓜科林的水解动力学和清除.
- 为了阐明涉及到阿雷卡坚果化物排毒的代谢途径和酶.
主要方法:
- 开发一种HPLC-UV生物分析方法,用于量化阿雷科林,瓜科林及其代谢物.
- 在人肝显微体 (HLM) 和细胞醇 (HLC) 中测定水解动力学和内在清除.
- 利用酶抑制剂来识别参与阿雷科林代谢的特定酶.
主要成果:
- 在阿雷科林水解之后,迈凯利斯-门动力学与高明显的内在清除 (Clint.in vivo) 在HLM (57.8毫升/分钟/公斤) 和HLC (11.6毫升/分钟/公斤).
- 瓜可林在HLM (0.654毫升/分钟/公斤) 和HLC (0.466毫升/分钟/公斤) 中显示出明显较低的水解速率和清除值.
- 亚雷科林被确定为碳氧乙酶1 (CES1) 的基质,而不是CES2.
结论:
- 阿雷科林在人体肝脏中经历了大量的水解,这表明有效的解毒.
- 观察到阿雷科林和瓜科林之间代谢清除率的显著差异.
- 碳氧乙酶1 (CES1) 在阿雷科林的肝脏代谢中起着关键作用.
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