知母皂苷对葛根素在正常、糖尿病大鼠体内药动学的影响

Effects of timosaponin on the in vivo pharmacokinetics of puerarin in normal and diabetic rats

目的考察知母皂苷对葛根素在正常、糖尿病大鼠体内药动学的影响。方法正常大鼠随机分为4组,分别灌胃给予葛根素(100 mg/kg)、葛根素-低、中、高剂量知母皂苷(50、100、200 mg/kg);糖尿病大鼠随机分为2组,分别灌胃给予葛根素(100 mg/kg)、葛根素-知母皂苷(100 mg/kg),于0.083、0.167、0.33、0.5、1、2、3、4、6、8、10、12、24 h采血,LC-MS/MS法检测葛根素血药浓度,计算主要药动学参数。结果在正常大鼠中,与葛根素比较,葛根素-各剂量知母皂苷AUC_(0~∞)、C_(max)升高(P<0.05,P<0.01),CL_(Z/F)降低(P<0.05,P<0.01)。糖尿病大鼠中葛根素AUC_(0~t)、AUC_(0~∞)、C_(max)低于正常大鼠中(P<0.05,P<0.01),CL_(Z/F)更高(P<0.01);与葛根素比较,葛根素-知母皂苷AUC_(0~t)、AUC_(0~∞)、C_(max)升高(P<0.01),T_(max)延长(P<0.05),CL_(Z/F)、V_(Z/F)降低(P<0.01)。结论知母皂苷可明显提高葛根素在正常、糖尿病大鼠体内血药浓度,改变其药动学特征。

AIM To investigate the effects of timosaponin on the in vivo pharmacokinetics of puerarin in normal and diabetic rats.METHODS The normal rats were randomly assigned into four groups and given intragastric administration of puerarin(100 mg/kg)and puerarin-low,medium,high doses(50,100,200 mg/kg)of timosaponin,respectively;the diabetic rats were randomly assigned into two groups and given intragastric administration of puerarin(100 mg/kg)and puerarin-timosaponin(100 mg/kg),respectively,after which blood collection was made at 0.083,0.167,0.33,0.5,1,2,3,4,6,8,10,12,24 h,LC-MS/MS was adopted in the plasma concentration determination of puerarin,and main pharmacokinetic parameters were calculated.RESULTS In the normal rats,puerarin-various doses of timosaponin demonstrated increased AUC_(0-∞),C_(max)(P<0.05,P<0.01)and decreased CL_(Z/F)(P<0.05,P<0.01)as compared with those of puerarin.Puerarin displayed lower AUC_(0-t),AUC_(0-∞)and C_(max)in the diabetic rats than those in the normal rats(P<0.05,P<0.01),along with higher CL_(Z/F) (P<0.01);compared with puerarin,puerarin-timosaponin exhibited increased AUC_(0-t),AUC_(0-∞),C_(max)(P<0.01),prolonged T_(max)(P<0.05)and decreased CL_(Z/F) and V_(Z/F)(P<0.01).CONCLUSION Timosaponin can obviously enhance the in vivo plasma concentration of puerarin in normal and diabetic rats,and change its pharmacokinetic characteristics.