中文摘要：

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。

英文摘要：

Objective To determine the influence of Radix Adenophorae coadministrated with Veratrum nigrum L.on cytochrome P450 isoforms CYP1A2,CYP3A4,CYP2C9 and CYP2C19 by Cocktail probe drugs in rats,thus explore the in vivo evidence of the imcompatibility of them from the perspective of drug-drug interactions.Methods 24 male wistar rats were randomly divided into Radix Adenophorae group,Veratrum nigrum L.group,combined group and blank control group,which were given Radix Adenophorae decoction（13.5g.kg-1）,Veratrum nigrum L.decoction（0.81g.kg-1）,co-decoction（14.31g.kg-1） and normal saline for 7 days,then injected the mixture of 4 probes through vena caudalis on the 8th day,and soon after the blood samples were obtained through extirpating the eyeballs at a series of time-points.HPLC method was used to determine the concentrations of probe drugs in rat plasma,and pharmacokinetic parameters were estimated by WinNolin5.2.The effects of test drugs on the activities of cytochrome P450 isoforms were judged indirectly by comparing the pharmacokinetic parameters of treated groups with those of control group.Results Compared with the blank control group,Veratrum nigrum L.was decreased AUC（0～t） of tolbutamide and increased its Vz;Radix Adenophorae were decreased AUC（0～∞） of caffeine,significantly decreased AUC（0～t）,AUC（0～∞） of tolbutamide,and was increased Vz,CL of tolbutamide,no significant difference of dapsone and omeprazole.Compared with the Veratrum nigrum L.group,combination could increase MRT（0～t） of dapsone,decrease AUC（0～t）,AUC（0～∞） of omeprazoleand,increase CL of it;Compared with the Radix Adenophorae group,combination could increase AUC（0～t） of omeprazole.Conclusion Compared with the blank control group,Veratrum nigrum L.can induce CYP2C19 activities;Radix Adenophorae can induce CYP1A2 and CYP2C9 activities significantly with no effect on the activities of CYP3A4 and CYP2C19.Compared with the Veratrum nigrum L.group,CYP3A4 activities were inhibited in combin