三七总皂苷和灯盏花素单用与联用时主要成分的药动学比较

目的考察三七总皂苷(主要成分为三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1、人参皂苷Rd)和灯盏花素(主要成分为野黄芩苷)复方粉针制剂在健康比格犬体内的药动学,并与单独使用三七总皂苷粉针或灯盏花素粉针时的药动学参数进行比较。方法建立检测给药后不同时间点的比格犬血样中三七总皂苷各组分及野黄芩苷浓度的液相色谱-串联质谱联用(LC-MS/MS)方法,计算各成分的药动学参数。结果单次给予复方粉针后,三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1、人参皂苷Rd及野黄芩苷的血浆消除半衰期(t1/2)分别为(1.08±0.30),(0.95±0.16),(1.40±0.39),(51.08±10.42),(64.84±17.70)及(2.00±0.88)h;峰浓度(Cmax)分别为(4641.00±758.84),(11325.00±1418.62),(1822.00±253.37),(39380.00±5644.03),(12964.00±2738.41)及(2669.00±841.79)ng·mL-1;血药浓度-时间曲线下面积(AUC0-∞)分别为(2832.31±308.38),(3454.00±473.08),(1210.80±161.06),(1360410.90±277244.88),(320529.65±101345.47),(450.68±90.50)ng·mL-1·h。与三七总皂苷粉针或灯盏花素粉针单次给药相比,复方粉针单次给药后,血药浓度-时间曲线相似;三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rd的Cmax显著升高(P<0.05);人参皂苷Rb1和野黄芩苷Cmax差异无统计学意义(P>0.05);t1/2、AUC0-∞差异无统计学意义(P>0.05)。结论三七总皂苷粉针和灯盏花素粉针联合用药可提高三七总皂苷部分组分的Cmax,对野黄芩苷的药动学没有明显影响。

Comparison of Pharmacokinetic Parameters of Main Components of Notoginseng Total Saponins and Breviscapine When Used Alone or in Combination

Objective To investigate the pharmacokinetics of the combination of notoginseng total saponins(main components are notoginsenoside R1,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,ginsenoside Rd)and breviscapine(main component is scutellarin)in healthy Beagle dogs,and compared with the pharmacokinetic parameters when using the notoginseng total saponins for injection or breviscapine for injection alone.Methods The LC-MS/MS method was established to determine the concentration of notoginseng total saponins and the concentration of scutellarin in the blood samples of Beagle dogs at different time points after drug administration.The pharmacokinetic parameters of each component were calculated.Results After a single dose of compound powder,the plasma elimination half-life(t1/2)of notoginsenoside R1,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,ginsenoside Rd and scutellarin were(1.08±0.30),(0.95±0.16),(1.40±0.39),(51.08±10.42),(64.84±17.70)and(2.00±0.88)h,respectively;peak concentration(Cmax)were(4641.00±758.84),(11325.00±1418.62),(1822.00±253.37),(39380.00±5644.03),(12964.00±2738.41)and(2669.00±841.79)ng·mL-1,respectively;the area under the curve(AUC0-∞)were(2832.31±308.38),(3454.00±473.08),(1210.80±161.06),(1360410.90±277244.88),(320529.65±101345.47)and(450.68±90.50)ng·mL-1·h,respectively.Compared with the single administration of notoginseng total saponins or breviscapine,the blood drug concentration-time curve was similar after a single administration of the compound powder;The Cmaxof notoginsenoside R1,ginsenoside Rg1,ginsenoside Re,and ginsenoside Rd was significantly increased(P<0.05);There was no significant difference in the Cmaxof ginsenoside Rb1and scutellarin(P>0.05);no significant difference in t1/2and AUC0-∞for all components(P>0.05).Conclusion The combination use of notoginseng total saponins for injection and breviscapine for injections can increase the Cmaxof some components of the notoginseng total saponins,but has no significant effect on the pharmacokinetics of scutellarin.