Effects of notoginsenoside R1 on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats by cocktail probe drugs
Effects of notoginsenoside R1 on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats by cocktail probe drugs
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鸡尾酒探针药物三七皂苷R1对大鼠CYP1A2、CYP2C11、CYP2D1和CYP3A1/2活性的影响
DOI：
10.3109/13880209.2015.1029051
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发表时间：
2016-02-01
影响因子：
3.8
通讯作者：
Liu, Gaofeng
中科院分区：
文献类型：
--
作者：
Yin, Shuo;Cheng, Yanwen;Liu, Gaofeng
摘要背景：三七皂苷R1(NGR1)是三七中具有心血管活性的主要成分。陈芳华，一种广泛用于增强血液循环和消除血瘀症的中草药。目的：利用细胞色素P450探针药物，观察神经生长因子1‘S对大鼠体内细胞色素P450、细胞色素P3A1/2活性的影响。材料和方法：大鼠经神经生长因子受体1或生理盐水预处理后，给予含咖啡因(10 mg/kg)、甲苯丁胺(15 mg/kg)、美托洛尔(20 mg/kg)和氨苯砜(10 mg/kg)的鸡尾酒探针药物混合液。然后在一组时间点采集血液，进行超高效液相色谱/串联质谱仪(UPLC-MS/MS)分析。结果：神经生长因子1可使咖啡因Cmax(43.13%，p <； )和AUC0 − ∞(40.57%，p <； 0.01)升高，CL/F降低(62.16%，p 和lt；与对照组比较，甲苯磺丁胺、美托洛尔和氨苯砜的药代动力学参数均无明显变化，说明 对大鼠的细胞色素P4502、细胞色素P4502和细胞色素P3A1/2无明显影响。讨论与结论：当神经生长抑素与细胞色素P450 1A2代谢的药物合用时，应监测相关的药物-药物相互作用。
Abstract Context: Notoginsenoside R1 (NGR1) is the main component with cardiovascular activity in Panax notoginseng (Burk.) F. H. Chen, an herbal medicine that is widely used to enhance blood circulation and dissipate blood stasis. Objective: The objective of this study is to investigate NGR1's effects on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats in vivo through the use of the Cytochrome P450 (CYP450) probe drugs. Materials and methods: After pretreatment with NGR1 or physiological saline, the rats were administered intraperitoneally with a mixture solution of cocktail probe drugs containing caffeine (10 mg/kg), tolbutamide (15 mg/kg), metoprolol (20 mg/kg), and dapsone (10 mg/kg). The bloods were then collected at a set of time-points for the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis. Results: NGR1 was shown to exhibit an inhibitory effect on CYP1A2 by increased caffeine Cmax (43.13%, p < 0.01) and AUC0 − ∞ (40.57%, p < 0.01), and decreased CL/F (62.16%, p < 0.01) in the NGR1-treated group compared with those of the control group, but no significant changes in pharmacokinetic parameters of tolbutamide, metoprolol, and dapsone were observed between the two groups, indicating that NGR1 had no effects on rat CYP2C11, CYP2D1, and CYP3A1/2. Discussion and conclusion: When NGR1 is co-administered with drugs that are metabolized by CYP1A2, the pertinent potential herb–drug interactions should be monitored.