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目的利用Cocktail探针法,测定南沙参与藜芦配伍对大鼠CYP1A2、CYP3A4、CYP2C9和CYP2C19酶活性的影响,从药物相互作用角度探寻二者配伍增毒相反的体内证据。方法将24只雄性Wistar大鼠随机分组,南沙参组、藜芦组、合用组分别灌胃南沙参煎液(13.5g.kg-1)、藜芦煎液(0.81g.kg-1)、合煎液(14.31g.kg-1),空白组灌胃生理盐水,连续给药7天,于第8天尾静脉注射混合探针药物后于不同时间点采集血样;血样经处理后利用HPLC同时测定不同时间点各探针药物的血药浓度,通过WinNolin5.2软件计算各探针药物的药动学参数,并进行组间比较,进而反映亚酶活性在各组之间的差异。结果与空白对照相比,藜芦组可降低甲苯磺丁脲的AUC(0～t),增加其Vz;南沙参组可降低咖啡因的AUC(0～∞),显著降低甲苯磺丁脲的AUC(0～t)、AUC(0～∞)并使其Vz,CL显著增加,对氨苯砜、奥美拉唑的各药动学参数无明显影响;与藜芦组相比,合用可增加氨苯砜的MRT(0～t),降低奥美拉唑的AUC(0～t),AUC(0～∞)并增加其CL;与南沙参组相比,合用可增加甲苯磺丁脲的AUC(0～t),降低其Vz,CL。结论与空白组相比,藜芦组对大鼠CYP2C9具有诱导作用,南沙参组对大鼠CYP1A2酶具有诱导作用,对CYP2C9酶具有显著诱导作用,对CYP3A4、CYP2C19无明显影响;与藜芦组相比,合用组对大鼠CYP3A4酶具有抑制作用,对CYP2C19酶具有诱导作用;与南沙参组相比,合用组对大鼠CYP2C19酶具有抑制作用。
Objective To determine the effects of Nansha on the activity of CYP1A2, CYP3A4, CYP2C9 and CYP2C19 in rats by Cocktail probe method. Methods Twenty-four male Wistar rats were randomly divided into three groups: nansha ginseng group, veratridine group, and combined group were given gavage of 13.5 g.kg-1, (14.31g.kg-1). The rats in the blank group were given normal saline by gavage for 7 consecutive days. Blood samples were collected at different time points after the intravenous injection of mixed probe drugs on the 8th day. The blood samples were processed by HPLC At the same time, the plasma concentration of each probe drug was measured at different time points. The pharmacokinetic parameters of each probe drug were calculated by WinNolin5.2 software and compared between groups, which reflected the differences in the activity of the enzyme between the groups. Results Compared with the blank control, veratridine group could reduce the AUC (0 ~ t) of tolbutamide and increase its Vz; Nansha ginseng group could reduce the AUC (0 ~ ∞) of caffeine and significantly reduce the tolbutamide AUC (0 ~ t), AUC (0 ~ ∞) and make it Vz, CL significantly increased, on dapsone, omeprazole pharmacokinetic parameters had no significant effect; compared with the veratrole group, Increasing the MRT (0 ~ t) of dapsone decreased the AUC (0 ~ t), AUC (0 ~ ∞) of omeprazole and increased its CL; compared with the nansha ginseng group, the combination could increase tolbutamide Of AUC (0 ~ t), reduce its Vz, CL. Conclusion Compared with the blank group, the veralex group has the induction effect on the rat CYP2C9, the Nansha ginseng group has the induction effect on the CYP1A2 enzyme, the CYP2C9 enzyme has a significant induction effect on CYP3A4, CYP2C19 no significant effect; Compared with the Nansha Ginseng group, the combination group had an inhibitory effect on the CYP3A4 enzyme and the CYP2C19 enzyme. Compared with the Nansha Ginseng group, the combined group had an inhibitory effect on the CYP2C19 enzyme.