新的合成阿片类药物 - - 班齐米达的代谢特征 - - 尼塔酶
Gajanan R Jadhav1, Pius S Fasinu1
1Department of Pharmacology and Toxicology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States.
Frontiers in pharmacology
|August 2, 2024
概括
新的合成阿片类药物称为尼塔,在人体肝脏中迅速代谢. 了解这种新陈代谢是检测尼塔中毒和评估成风险的关键.
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
- 药用化学 医学化学
背景情况:
- 来自本齐米达化学品组的新合成阿片类药物 (NSO) 类别尼塔重新浮出水面,引起了公众健康的担忧.
- 由于滥用潜力很高,它们的发展在20世纪60年代被停止,因此对它们的新陈代谢和生理影响的知识有限.
研究的目的:
- 为了研究三种尼塔的体外代谢和处置:布托尼塔,异尼塔和质尼塔.
- 为了确定参与尼塔代谢的主要细胞P450 (CYP) 酶.
主要方法:
- 用人类肝脏显微体 (HLM),人类S9 (HS9) 分数和复合性CYP酶化布托尼塔,异尼塔和原尼塔.
- 使用特定的CYP酶来确定它们在尼塔代谢中的作用的代谢表型化.
主要成果:
- 这三种尼塔都在HLM和HS9分量中经历了快速代谢 (在60分钟内95%的耗尽) .
- 在所有测试的尼塔中,观察到高的体外内在清除值 (CLint),超过了维拉帕米尔和的值.
- 代谢涉及氧化,脱基化和脱甲基化途径,主要由CYP2D6,CYP2B6和CYP2C8.8进行介导.
结论:
- 尼塔因由主要的人类肝脏CYP酶,特别是CYP2D6.6迅速代谢.
- 快速的新陈代谢可能会影响在法医和临床毒理学中检测和量化不变的尼塔.
- 在CYP酶中的多态性可能会影响个体对尼塔中毒和成的敏感性.
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