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中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (5): 509-513.

• 研究原著 • 上一篇    下一篇

米氮平在鼠肝微粒体中的体外代谢研究

陈磊, 肖红1, 刘文英   

  1. 中国药科大学药分教研室, 南京 210009, 江苏;
    1南京脑科医院临床药理室, 南京 210029, 江苏
  • 收稿日期:2005-03-08 修回日期:2005-04-18 出版日期:2005-05-26 发布日期:2020-11-19
  • 通讯作者: 刘文英,女, 教授, 博士生导师, 研究方向:药物色谱分析。Tel:025-83271251 E-mail:wycpu@tom.com
  • 作者简介:陈磊, 女, 在读硕士, 研究方向:药物色谱分析。Tel:025-83271251   E-mail:chenlei_no@hotmail.com; 肖红, 女, 主任药师, 研究方向:临床药理。Tel:025-83906782
  • 基金资助:
    2004 南京市科技发展计划项目立项项目

Research of metabolism of antidepressant mirtazapine on mice liver micro-some in vitro

CHEN Lei, XIAO Hong1, LIU Wen-ying   

  1. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing210009, Jiangsu, China;
    1Depart-ment of Pharmacology Nanjing Brain Hospital, Nanjing210029, Jiangsu, China
  • Received:2005-03-08 Revised:2005-04-18 Online:2005-05-26 Published:2020-11-19

摘要: 目的: 通过不同诱导剂预处理鼠肝, 研究米氮平在肝微粒体中的代谢主要受何种酶影响, 同时研究米氮平对介导其自身代谢的 P450 酶亚型是否有影响, 为米氮平的临床合理应用提供科学依据。方法: 将米氮平与不同诱导剂诱导的鼠肝微粒体进行体外孵育代谢, 以乙腈中止反应, 样品用 25%氨水碱化后以环己烷提取。用 RP-HPLC 测定剩余的米氮平含 量, 流 动相为 甲醇 :水 (含 10 mmol°L-1NH 4 AC, 5 mmol°L-1SDS, pH 3.5) 62 :38(V/V), 检测波长为 307 nm。结果: 本文测定方法回收率高,日内和日间精密度均良好, 符合生物样本检测要求。苯巴比妥诱导的鼠肝微粒体对米氮平的代谢具有明显的催化作用, 利福平也有一定的催化能力, 米氮平诱导的鼠肝微粒体与对照组对米氮平的代谢无明显差异。结论: 由苯巴比妥诱导的 P450 酶亚型(主要为细胞色素P450 3A4) 和利福平诱导的 P450 酶亚型(主要为细胞色素 P450 2C9/2C19, 同时也对 P4503A4 有一定的诱导作用) 在米氮平的体外代谢中起着重要作用;而米氮平诱导组对于米氮平代谢无明显影响, 预示米氮平对介导其自身代谢的 P450 酶亚型无明显的诱导或抑制作用。

关键词: 米氮平, 高效液相色谱, 肝微粒体, 体外代谢

Abstract: AIM: To identify the isoforms of cyto-chrome P450 (CYP) involved in the metabolism of mir-tazapine and the influence of mirtazapine on the me-tabolism of mirtazapine. METHODS: Mirtazapine was incubated with rats liver microsomes induced by different inducers, and the reaction was terminated by acetonitrile. The sample was added 25%ammonia water and extracted with cyclohexane, and the determination was performed by RP-HPLC with the mobile phase of methanol-water (including 10 mmol°L-1 NH 4 AC, 5 mmol°L-1 SDS, pH 3.5) 62 :38(V/V). RESULTS: The assay was linear from 75.3 to 565 μmol°L-1 for mirtazapine in rat hepatic microsomal incubates.The livers induced by phenobarbi-tal were catalyzed and livers induced by rifampicin also showed more active performance, while the livers induced by rats had no significant difference between two groups. CONCLUSION: P450 3A4 induced by phenobarbital as well as rifampicin is crucial in the metabolism of mirtaza-pine. And P450 2C9/2C19 induced by rifampicin may al-so interfere the metabolism of mirtazapine. Mirtazapine has no obvious effect on the isoforms responsible for its metabolism of mirtazapine.

Key words: KEY WOEDS mirtazapine, HPLC, liver microsomes, in vitro metabolism

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