Cocktail探针药物法评价羊耳菊对大鼠CYP450酶活性的影响  

Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs

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作  者:宋菲 杨健 王春 王霞 李维维 潘洁 兰燕宇 刘亭 SONG Fei;YANG Jian;WANG Chun;WANG Xia;LI Wei-wei;PAN Jie;LAN Yan-yu;LIU Ting;State Key Laboratory of Functions and Applications of Medicinal Plants,Provincial Key Laboratory of Pharmaceutics in Guizhou Province,Engineering Research Center for Development and Application of Ethnic Medicine and Traditional Chinese Medicine,Ministry of Education,School of Pharmaceutical Sciences,Guizhou Medical University

机构地区:贵州医科大学药用植物功效与利用国家重点实验室贵州省药物制剂重点实验室民族药与中药开发应用教育部工程研究中心药学院

出  处:《中国实验方剂学杂志》2019年第2期60-67,共8页China Journal of Experimental Traditional Medical Formulae

基  金:国家自然科学基金项目(81360680,81760699);贵州省科学技术厅人才团队项目(黔科合平台人才[2016]5613/5677);贵阳市科研创新团队项目(筑科合同[2017]30-29号)

摘  要:目的:采用Cocktail探针药物法考察羊耳菊活性部位提取物(以下均简称为羊耳菊)对6种大鼠细胞色素P450(CYP450)主要亚型酶活性的影响。方法:羊耳菊高、低剂量组大鼠给药剂量分别为8. 127,2. 709 g·kg-1·d-1(以生药量计算),分别连续灌胃7,14 d后尾静脉注射Cocktail探针药物咖啡因、咪达唑仑、甲苯磺丁脲、奥美拉唑、美托洛尔和氯唑沙宗,不同时间点采集血样,建立超高效液相串联质谱法(UPLC-MS)测定大鼠血浆中6种探针药物的浓度,运用DAS 2. 0软件计算其药动学参数,以考察羊耳菊在大鼠体内对CYP1A2,CYP3A,CYP2C9,CYP2C19,CYP2D6,CYP2E1这6种亚型酶代谢活性的影响。结果:与空白组相比,奥美拉唑指标下,给药组的药时曲线下面积AUC0-t和AUC0-∞增大,14 d给药组的半衰期(T1/2)增大,清除率(CL)降低;甲苯磺丁脲指标下,14 d高剂量组的AUC0-t,AUC0-∞和T1/2增大;咖啡因指标下,给药组的T1/2明显增大,14 d给药组的AUC0-t和AUC0-∞增大而CL降低;但以上3个指标的表观分布容积(V)均无明显变化。与空白组相比,咪达唑仑指标下,除7 d低剂量组之外,其他给药组的AUC0-t,AUC0-∞和T1/2明显增大,CL明显降低,V增大;氯唑沙宗和美托洛尔的药动学参数与空白组相比差异没有显著性。结论:羊耳菊对大鼠肝药酶CYP3A,CYP1A2,CYP2C9和CYP2C19的活性具有不同程度的抑制作用,其中对CYP3A的抑制作用最强。Objective: To study on the effect of Inula cappa extract on the activities of six cytochrome P450( CYP450) enzymes in rats by Cocktail probe method. Method: Rats in the I. cappa high and low dose groups were given oral administration of active fractions of I. cappa at a dose of 8. 127,2. 709 g·kg-1·d-1 of the material for 7,14 d,repectively. Probe drugs( caffeine,midazolam,tolbutamide,omeprazole,metoprolol,chlorzoxazone) were simultaneously injected to rats after administration. Plasma was collected at different time after the administration of probe drugs. The plasma concentrations of these six probes were measured by UPLC-MS and their corresponding pharmacokinetic parameters were calculated with DAS 2. 0. Result: Compared with the control group,only the apparent volume of distribution( V) of midazolam was increased; area under the curve( AUC0-t and AUC0-∞) and half-life period( T1/2) of caffeine,midazolam,tolbutamide and omeprazole were increased and the clearance rate( CL) of them was decreased in rats of I. cappa groups. But there were no differences in pharmacokinetic parameters of chlorzoxazone and metoprolol. Conclusion: I. cappa can reduce the enzymatic activities of CYP3A,CYP1A2,CYP2C9 and CYP2C19 in rats at different degree,among which CYP3A is the strongest.

关 键 词:COCKTAIL探针药物法 羊耳菊 活性部位 提取物 细胞色素P450 药物相互作用 咪达唑仑 

分 类 号:R285.5[医药卫生—中药学;医药卫生—中医学]

 

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