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目的用“cocktail”探针药物法研究单次或多次口服辣椒素对大鼠肝药酶CYP1A2、CYP2C11和CYP3A的影响。方法将雄性SD大鼠随机分组,给予辣椒素25 mg.kg-1,分别灌胃1,3,7 d,以0.5%羧甲基纤维素钠作为空白对照组,每组8只,给药后于不同的时间点采集血样。用HPLC测定大鼠血浆中探针药物咖啡因、甲苯磺丁脲和氨苯砜的浓度,血药浓度-时间数据采用DAS2.1.1软件进行药动学分析。结果与对照组相比,辣椒素灌胃7 d后,咖啡因的AUC0-t、AUC0-∞和ρmax显著减小,CL/F显著增大;甲苯磺丁脲的AUC0-t显著减小,ρmax极显著减小;氨苯砜的AUC0-t和AUC0-∞极显著减小,CL/F和V/F极显著增大。结论辣椒素灌胃7 d后对大鼠肝药酶CYP1A2、CYP2C11和CYP3A可能存在不同程度的诱导作用,其中对CYP3A的诱导作用较强。
Objective To study the effect of single or multiple oral administration of capsaicin on the hepatic drugs CYP1A2, CYP2C11 and CYP3A in rats by using “cocktail” probe drug method. Methods Male Sprague-Dawley rats were randomly assigned to receive capsaicin (25 mg · kg-1) for 1, 3 and 7 d, and 0.5% sodium carboxymethylcellulose was used as a blank control group, with 8 rats in each group. Blood samples were collected at different time points. The concentrations of caffeine, tolbutamide and dapsone in rat plasma were determined by HPLC. The plasma concentration-time data were analyzed by DAS2.1.1 software. Results Compared with the control group, the AUC0-t, AUC0-∞ and ρmax of caffeine were significantly decreased and the CL / F of caffeine was significantly increased after the capsaicin was administered for 7 days. The AUC0-t of tolbutamide was significantly decreased, ρmax was significantly reduced; AUC0-t and AUC0-∞ of dapsone significantly decreased, while CL / F and V / F significantly increased. Conclusion Capsaicin can induce different degrees of CYP1A2, CYP2C11 and CYP3A in rats after 7 days of gavage, and the induction of CYP3A is stronger.