大明胶囊对大鼠体内细胞色素P450酶活性的影响

Effect of Daming Capsules on Activity of Cytochrome P450 in Rats

目的用Cocktail探针药物法研究大明胶囊对大鼠体内细胞色素P450酶活性的影响。方法将大鼠随机分组,低剂量和高剂量组分别给予大明胶囊50、100 mg.kg-1,空白对照组给予生理盐水,通过HPLC测定探针药物的血药浓度并计算其药动学参数,评价大明胶囊对相应大鼠细胞色素P450酶活性的影响。结果低剂量和高剂量组中美托洛尔、氯唑沙宗和甲苯磺丁脲的药动学参数与空白对照组相比无显著性差异;高剂量组中咖啡因和奥美拉唑AUC,t1/2,ρmax显著增加,Vd/F和CL/F明显降低,tmax无明显变化,低剂量组各参数与空白对照组无显著性差异;低剂量和高剂量组中氨苯砜AUC,t1/2,ρmax显著增加,Vd/F和CL/F明显降低,tmax无明显变化。结论大明胶囊对大鼠CYP3A4有抑制作用,对CYP2C9、CYP2D6和CYP2E1无显著影响,高剂量大明胶囊对CYP1A2和CYP2C19有抑制作用,低剂量则无明显影响。

OBJECTIVE To study the influence of Daming Capsules on cytochrome P450 activity in rats by using a ＂Cocktail＂ ap- proach. METHODS Rats were randomly divided into high-dose, low-dose and control groups. The rats in high-dose and low-dose groups were given 100 and 50 mg · kg^-1 Darning Capsules, respectively, while the rats in the control group were given saline. The plasma concentrations of the probes were determined by HPLC methods. RESULTS There were no significant differences in plasma concentra- tions and pharmacokinetic parameters of tolbutamide, metoprolol and chlorzoxazone between the control group and the test groups. Com- pared with the control group, high-dose Daming Capsules significantly increased the AUC, t~/2 and p and significantly decreased the Vd/F and CL/F of caffeine and omeprazole. However, low-dose Daming Capsule did not induce significant changes in plasma concentra- tions and pharmacokinetic parameters of caffeine and omeprazole. The rats in high-dose and low-dose groups had higher AUC, t1/2 and Pmax, and lower Vd/F and CL/F for dapsone, compared with those in the control group. CONCLUSION The results suggest that highdose and low-dose Daming Capsules inhibit CYP3A4 activity, however, they have no effects on CYP2C9, CYP2D6 and CYP2E1. In addi- tion, the activity of CYP1A2 and CYP2C19 can be inhibited by high-dose, but not low-dose Daming Capsules.