三七总皂苷注射液对大鼠肝CYP450酶的影响

目的：在体酶探针法研究三七皂苷注射液对大鼠肝CYP450酶的影响。方法：连续5周静脉注射给予大鼠20mg·kg^-1·d^-1的三七总皂苷注射液后分别静注5．0mg／kg的尼莫地平或灌胃20．0mg／kg的华法林钠，HPLC法测定尼莫地平和华法林钠的血浆药物浓度，DAS软件计算药动学参数，评价三七总皂苷注射液对大鼠CYP3A4、CYP2C9和CYP1A2酶的影响，采用双侧t检验方法对数据进行分析。结果：建立并优化了大鼠体内尼莫地平和华法林钠的高效、快速和专属性强的HPLC测定方法，三七总皂苷注射液对尼莫地平和华法林钠在大鼠体内的药动学参数无显著性影响，但长时间给予三七总皂苷注射液后有致尼莫地平AUC升高而清除率下降的趋势，也使华法林钠在大鼠体内的tmax、t1/2小AUC有升高的趋势。结论：三七总皂苷对CYP3A4、CYP2C9和CYP1A2可能有一定的抑制作用，提示我们在临床上与上述酶底物合用时应注意药物相互作用出现的可能性．

Experimental study on the effects of liver cytochrome protein 450(CYP450)induced by panax notoginsenoside injection in rats

AIM:Enzymes probes were employed for the study on the effects of liver CYP450 induced by panax notoginsenoside injection(PNSi)in rats.METHODS:PNSi was intravenous administered to rats for 5 weeks at the dosage of 20 mg·kg~(-1)·d~(-1).Then 5.0 mg/kg dosage of nimodipine or 20.0 mg/kg dosage of warfarin sodium was given to rats via intravenous or intragastric administration,respectively at the last time of PNSi.HPLC was employed for the determination of nimodipine and warfarin sodium in rat plasma.Pharmacokinetic parameters which simulated by DAS software were used for the evaluation on the effects of CYP3A4,CYP2C9 and CYP1A2 induced by PNSi.Two-sides of students test was used for datum analysis.RESULTS:Sensitive,rapid and specificity HPLC method was developed and validated for the determination of nimodipine and warfarin in rat plasma successfully.There were no markedly changes of pharmacokinetic parameters of nimodipine or warfarin in rats induced by PNSi.However,the AUC and clearance of nimodipine displayed the tendency of increasing or decreasing,respectively and the t_(max),t_(1/2) and AUC of warfarin sodium showed the tendency of increasing after intravenous administration of PNSi for a long time.CONCLUSION:PNSi showed potential inhibitory effect on the activities of CYP3A4,CYP2C9 and CYP1A2.Potential drug-drug interaction should be more cared when PNSi was co-administered with nimodipine or warfarin sodium in clinic.