摘要
采用Cocktail探针药物法研究玄参对大鼠4种细胞色素P450(CYP3A4、CYP2D6、CYP2C9和CYP1A2)活性的影响.24只健康雄性SD大鼠(Sprague-Dawley rat)随机分为三组:A组为多剂量组,连续7 d给予150 mg/kg玄参.B组为单剂量组,第7 d给予150 mg/kg玄参.C组为对照组.第7 d,各组在给予玄参30 min后,再给予4种探针药物的混合溶液,其中咪达唑仑3 mg/kg、美托洛尔20 mg/kg、氯沙坦5 mg/kg、非那西汀5 mg/kg,分别用以评价CYP3A4、CYP2D6、CYP2C9和CYP1A2的活性.根据设定的时间点收集大鼠血浆样品,处理后的样品采用超高效液相色谱-串联质谱(UHPLC-MS/MS)法测定样品中4种探针药物的浓度.结果可见,玄参对大鼠体内氯沙坦和非那西汀的药代动力学参数无显著影响.单剂量的玄参导致咪达唑仑代谢减慢,多剂量给予的玄参显著诱导美托洛尔代谢.玄参对CYP2C9和CYP1A2的酶活性无明显影响,可以抑制CYP3A4或诱导CYP2D6的酶活性.
The effects of Scrophularia ningpoensis on the activities of 4 Cytochrome P450 enzymes(CYP3A4,CYP2D6,CYP2C9 and CYP1A2)in rats was investigated using the Cocktail probe drug method.Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups:group A(multiple-doses of 150 mg/kg Scrophularia ningpoensis for 7 d),group B(single-dose of 150 mg/kg Scrophularia ningpoensis),and group C(control group).To each group after administering Scrophularia ningpoensis for 30 min,the mixture solution of probe drugs midazolam(3 mg/kg,evaluation of CYP3A4 activity),metoprolol(20 mg/kg,evaluation of CYP2D6 activity),losartan(5 mg/kg,evaluation of CYP2C9 activity)and phenacetin(5 mg/kg,evaluation of CYP1A2 activity)were administered orally on the 7th d.Rat plasma samples were collected at the arranged time points,and the plasma concentrations of 4 probe drugs in the samples were simultaneously determined using the ultra-high performance liquid chromatography tandem mass spectrometry(UHPLC–MS/MS)method after processing.The results showed that Scrophularia ningpoensis had almost no significant effect on the pharmacokinetic parameters of losartan and phenacetin.However,a single-dose of Scrophularia ningpoensis induced a slow metabolism of midazolam.In addition,the pharmacokinetics of metoprolol was affected significantly by the multiple doses of Scrophularia ningpoensis,which induced rapid metabolism.The results suggested that Scrophularia ningpoensis has no significant effect on the enzymatic activities of CYP2C9 and CYP1A2,but it might inhibit enzymatic activities of CYP3A4 or induce CYP2D6.
作者
魏艳丽
应晓倩
谈文状
吴美玲
江悦娟
丁明星
杜洪建
WEI Yani;YING Xiaoqian;TAN Wenzhuang;WU Meiing;JIANG Yuejuan;DING Mingxing;DU Hongjian(Jinhua Polytechnic,Jinhua 321007,Zhejiang China)
出处
《分析测试技术与仪器》
CAS
2023年第1期76-82,共7页
Analysis and Testing Technology and Instruments
