注射用益气复脉(冻干)在正常和慢性心衰大鼠体内的药动学研究

Pharmacokinetic study on Yiqi Fumai Lyophilized Injection in normal and CHF model rats in vivo

目的研究注射用益气复脉(冻干,YQFM)中10种人参皂苷成分(Rg1、Rb1、Rc、Rd、Re、Rf、Rg3、Rh1、Rb2和Rb3)在正常和慢性心力衰竭模型大鼠体内的药动学规律与差异,为其临床合理用药提供参考。方法 12只Wistar大鼠随机分为对照组和模型组,每组6只。采用冠状动脉结扎法建立慢性心衰大鼠模型,造模14 d后,两组大鼠均iv给予YQFM543 mg/kg。建立超高效液相色谱-质谱联用(UFLC-MS/MS)法,测定不同时间点各人参皂苷的血药浓度,绘制药时曲线,采用DAS 3.0药动学软件计算药动学参数,并进行比较。结果 iv YQFM后,各皂苷成分在对照组和慢性心力衰竭模型组大鼠体内的主要药动学参数T_(1/2)、AUC_(0-t)、AUC_(0-∞)、CL等,均没有显著性差异。结论在慢性心力衰竭状态下,机体对YQFM中皂苷成分的代谢无明显影响。

Objective To study the rule and difference of pharmacokinetics of ten ginsenosides（Rg1, Rb1, Rc, Rd, Re, Rf, Rg3, Rh1,Rb2 and Rb3） in Yiqi Fumai Lyophilized Injection（YQFM） in normal and chronic heart failure（CHF） model rats in vivo, and provide reference for clinical rational drug use. Method Totally twelve Wistar rats were randomly divided into control and model group（n=6）, chronic heart failure model of rats was established by using coronary artery ligation method. At 14 d after modeling, all rats in the two groups were given iv administration of YQFM（543 mg/kg）. The plasma concentration of ginsenosides at different time-points was analyzed by Ultra high performance liquid chromatography-mass spectrometry（UFLC-MS/MS）, the drug-time curves were drawn and the pharmacokinetic parameters were calculated and compared by DAS 3.0 program. Results The main pharmacokinetic parameters of ginsenosides in the CHF model group, such as T1/2, AUC0-t, AUC0-∞, CLz, had no significant difference compared with control group after administration of YQFM. Conclusion The body has no significant effect on the metabolism of ginsenosides in the condition of chronic heart failure.