甲基原薯蓣皂苷对人肝微粒体中7种CYP450酶活性的影响  被引量:8

Effect of methyl protodioscin on seven cytochrome P450s activities in human microsomes

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作  者:曹秀珍[1] 张伟[2] 姚志红[3] 谭志荣[2] 周宏灏[2] 姚新生[1] 

机构地区:[1]沈阳药科大学中药学院,辽宁沈阳110016 [2]中南大学临床药理研究所,湖南长沙410078 [3]暨南大学中药及天然药物研究所,广东广州510632

出  处:《沈阳药科大学学报》2008年第11期914-918,共5页Journal of Shenyang Pharmaceutical University

摘  要:目的研究甲基原薯蓣皂苷对CYP450酶的7种亚型酶活性的影响。方法将MPD和CYP450酶7种亚型的特异性探针底物咖啡因(CYP1A2)、右美沙芬(CYP2D6)、甲苯磺丁脲(CYP2C9)、s-美芬妥因(CYP2C19)、氯唑沙宗(CYP2E1)、香豆素(CYP2A6)及咪达唑仑(CYP3A4)与人肝微粒体进行孵化反应,采用HPLC和LeMS/MS法测定对应的7种代谢产物(1,7-二甲基黄嘌呤、去甲右美沙芬、4-羟基甲苯磺丁脲、4-羟基美芬妥因、6-羟基氯唑沙宗、7-羟基香豆素和1-羟基咪达唑仑)的浓度,通过与对照组比较,确定MPD对以上7种酶活性的影响。结果MPD在1~10μmol·L^-1时对7种酶均无明显抑制作用,在100/μmol·L^-1时对CYP2D6有抑制趋势,但对其他6种酶无抑制作用,均无统计学意义(P〉0.05)。结论MPD在与以上6种酶(CYP1A2、CYP2E1、CYP2C19、CYP3A4、CYP2C9和CYP2A6)代谢的药物联合用药时,发生药物相互作用的可能性较小。Objective To investigate the effect of methyl protodioscin (MPD) on seven cytochrome P450 en- zymes in human liver microsome. Methods Seven probe drugs were incubated with or without methyl proto-dioscin respectively in human microsomes. The specific substrates used in this study were caffeine (CYP1A2), dextromethorphan ( CYP2D6 ), tolbutamide (CYP2C9), (s)-mephenytoin (CYP2C19), chlor zoxazone (CYP2E1), coumarin (CYP2A6) and midazolam (CYP3A4). The concentrations of the substrate metabolites (paraxanthine, dextrorphan, 4-hydroxytolbutamide, 4-hydroxymephenytoin, 6-hydroxychlor-zoxazone, 7-hydroxycoumarin and 1-hydroxymidazolam) were determined by HPLC and LC-MS/MS. Results MPD (1-10 μmol·L^-1) had no significant inhibition on the activities of the seven cytochrome P450 enzymes. MPD (100 μmol·L^-1) had inhibition tendency on the activity of CYP2D6 and no inhibition on the other six CYPs. No significant difference was observed (P 〉 0.05). Conclusions The probability of drug-drug interactions between MPD and other drugs, which are ( CYP1A2, CYP2E1, CYP2C19, CYP3A4, CYP2C9 and CYP2A6), is metabolized by the above six CYPs very low.

关 键 词:甲基原薯蓣皂苷 CYP450酶 人肝微粒体 抑制 

分 类 号:R94[医药卫生—药剂学]

 

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