抗肿瘤活性物CH330331在大鼠肝微粒体代谢及对药酶影响作用的研究

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (6): 607-612.

抗肿瘤活性物CH330331在大鼠肝微粒体代谢及对药酶影响作用的研究

孙海燕¹, 和凡², 毕惠嫦², 黄文林³, 黄民²

¹深圳职业技术学院,深圳 518055,广东;
²中山大学药学院临床药理研究所,广州 510080,广东;
³中山大学肿瘤防治中心,广州 510080,广东

收稿日期:2010-01-15 修回日期:2010-04-05 出版日期:2010-06-26 发布日期:2020-09-16
通讯作者: 黄民,男,教授,博士生导师,研究方向:药物代谢与药代动力学、遗传药理学。 Tel: 020-87334521 E-mail: huangmin@mail.sysu.edu.cn
作者简介:孙海燕,女,博士,副教授,研究方向:药物代谢与药代动力学。Tel: 0755-26019169 E-mail: haiyansun2000@yahoo.com.cn
基金资助:
国家科技重大专项经费资助(2009Z1X09304-003)

Studies on the metabolism and effect on the CYP450 of CH330331 in rat liver microsomes

SUN Hai-yan¹, HE Fan², BI Hui-chang², HUANG Wen-lin³, HUANG Min²

¹ Department of Applied Chemistry and Biotechnology, Shenzhen Polytechnic, Shenzhen 518055, Guangdong, China;
² Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China;
³ Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510080, Guangdong, China

Received:2010-01-15 Revised:2010-04-05 Online:2010-06-26 Published:2020-09-16

摘要/Abstract

摘要： 目的: 体外研究大鼠肝微粒体中CH330331代谢的酶促动力学,并利用“Cocktail”探针药物模型,研究CH330331对主要CYP450亚型的体外抑制作用。方法: 优化CH330331在大鼠肝微粒体中孵育的条件,并进行酶促动力学研究;探讨体外“Cocktail”探针药物模型的组成,并研究CH330331对CYP450亚型的体外抑制作用。结果: CH330331代谢的酶促动力学参数:最大反应速率(V_max)为2.08 μmol/(min·mg protein),米氏常数(K_m)为18.96 μmol/L。CH330331对大鼠CYP1A2、CYP2C9和CYP2D6有弱抑制作用,对大鼠CYP2C19、CYP2E1和CYP3A4没有抑制作用。结论: 临床使用中CH330331可以增加主要通过CYPCYP1A2,CYP2C9和CYP2D6代谢的药物浓度。

关键词: CH330331, 肝微粒体, CYP450, Cocktail

Abstract: AIM: To study the metabolic kinetics of CH330331 in rat liver microsome, and its inhibition on CYP450 subtypes in the “cocktail” models. METHODS: The incubation parameters in rat liver microsome were optimized and were the Michaelis-Menten parameters K_m and V_max estimated the component of probe inhibitors in “cocktail” models were also confirmed and the effect of CH330331 on main subtypes of cytochrome P450 studied. RESULTS: The K_m and V_max of CH330331 were 18.96 μmol/L and 2.08 μmol/(min·mg protein), respectively. CH330331 had a weakly inhibition to the activity of CYP1A2, CYP2D6 and CYP2C9 but had no effect on CYP2C19, CYP2E1, and CYP3A4. CONCLUSION: CH330331 can increase the blood concentration of those drugs that are metabolized mainly by CYP1A2, CYP2D6 and CYP2C9.

Key words: CH330331, Liver microsomes, CYP450, Cocktail

中图分类号:

R969

孙海燕, 和凡, 毕惠嫦, 黄文林, 黄民. 抗肿瘤活性物CH330331在大鼠肝微粒体代谢及对药酶影响作用的研究[J]. 中国临床药理学与治疗学, 2010, 15(6): 607-612.

SUN Hai-yan, HE Fan, BI Hui-chang, HUANG Wen-lin, HUANG Min. Studies on the metabolism and effect on the CYP450 of CH330331 in rat liver microsomes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(6): 607-612.

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