Cocktail探针药物法评价丹参注射液和心可舒片对家兔CYP450酶5种亚型的作用

发布时间：2018-03-21 19:05

本文选题：细胞色素P　切入点：混合探针底物法　出处：《中国药学杂志》2015年10期 　论文类型：期刊论文

【摘要】：目的采用"Cocktail"探针药物法考察丹参注射液和心可舒片对家兔CYP酶5种亚型CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4代谢的影响。方法将16只雄性家兔同时空腹给予混合探针药咖啡因、甲苯磺丁脲、奥美拉唑、右美沙芬和咪达唑仑,采用LC-MS/MS检测特定时间点的探针药物代谢率(代谢产物浓度与探针原型药物浓度的比值)。家兔随机分为丹参注射液组和心可舒片组,设计为自身对照实验,分3个周期,按顺序分别给药丹参低剂量组(0.5 m L·kg-1)、中剂量组(1 m L·kg-1)、高剂量组(2 m L·kg-1)和心可舒低剂量组(90 mg·kg-1)、中剂量组(180 mg·kg-1)和高剂量组(360 mg·kg-1)。每个周期经7 d洗净期后,连续给药7 d,第15天再给予探针药物后测代谢率。采用ANOVA方差分析比较各剂量组家兔和用药前探针药物的代谢率的变化。结果与用药前相比,各剂量组的混合探针药物代谢率均有下降趋势。结论丹参注射液、心可舒片使用7 d后可能抑制家兔体内CYP450酶代谢,与体外实验结果一致。这些药物与经过CYP450酶代谢的药物联合应用时,可能会引起药物相互作用,临床联合使用应提高警惕。
[Abstract]:Objective to investigate the effects of Salvia miltiorrhiza injection and Xinkesu tablet on the metabolism of CYP2C19 CYP2D6 and CYP3A4 in five subtypes of CYP enzymes in rabbits by "Cocktail" probe method. Methods 16 male rabbits were treated with caffeine, tolbutylurea and omeprazole on an empty stomach. Dextromethorphan and midazolam were used to detect the metabolic rate of probe drug (the ratio of metabolite concentration to probe prototype drug concentration) at a specific time point by LC-MS/MS. Rabbits were randomly divided into Danshen injection group and Xinkesu tablet group. Three cycles were divided into three periods: Danshen low dose group (0.5 mg / kg -1), middle dose group (1 mg / kg -1), high dose group (2 mg / kg -1), Xinkesu low dose group (90 mg kg -1), medium dose group (180 mg kg -1) and high dose group (360 mg kg -1). ANOVA variance analysis was used to compare the changes of the metabolic rate of the probe drugs in rabbits and before and after the administration of the drug for 7 days, and the results were compared with those before the administration of the drug, and the results showed that the metabolic rate of the probe drug was higher than that of the control group before and after the administration of the drug. Conclusion Salvia miltiorrhiza injection and Xinkeshu tablet may inhibit the metabolism of CYP450 enzyme in rabbits after 7 days of treatment. These drugs may cause drug interaction when combined with drugs metabolized by CYP450 enzymes.
【作者单位】：复旦大学附属华山医院药剂科;复旦大学附属华东医院药剂科;山东省千佛山医院药剂科;上海市徐汇区中心医院中心实验室;
【分类号】：R965

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