葛根芩连汤对吡格列酮在大鼠体内药动学行为的影响

目的考察葛根芩连汤对吡格列酮在大鼠体内药动学行为的影响。方法实验大鼠随机分成吡格列酮组和葛根芩连汤+吡格列酮组,每组6只,分别给予单次灌胃给药(生理盐水或14 g/kg葛根芩连汤,30 min后3 mg/kg吡格列酮)和多次灌胃给药(生理盐水或14 g/kg葛根芩连汤,每天1次,连续7 d,第8天生理盐水或14 g/kg葛根芩连汤,30 min后3 mg/kg吡格列酮)。LC-MS/MS法测定吡格列酮血药浓度,计算药动学参数。结果多次给药后,葛根芩连汤+吡格列酮组AUC、MRT_0～_t、C_max、T_max显著高于吡格列酮组(P<0.05,P<0.01),CL_z/F显著降低(P<0.01);较单次给药MRT_0～_t、t_1/2明显增加,CL_z/F明显降低,AUC_0～_t、C_max分别升高了1.81、2.13倍。结论葛根芩连汤多次给药较单次给药可提高吡格列酮在大鼠中的总体暴露水平。

Effects of Gegen Qinlian Decoction on pharmacokinetic behaviors of pioglitazone in rats

AIM To investigate the effects of Gegen Qinlian Decoction on pharmacokinetic behaviors of pioglitazone in rats. METHODS Expermental rats were randomly divided into pioglitazone group and Gegen Qinlian Decoction+pioglitazone group, 6 rats in each group, single intragastric administration (normal saline or 14 g/ kg Gegen Qinlian Decoction, followed by 3 mg/ kg pioglitazone after 30 min) and multiple intragastric administration (normal saline or 14 g/ kg Gegen Qinlian Decoction, once a day, for successive 7 days, followed by normal saline or 14 g/ kg Gegen Qinlian Decoction on the 8th day, and 3 mg/ kg pioglitazone after 30 min) were given, respectively. After the plasma concentration determination of pioglitazone by LC-MS/ MS, the calculation of pharmacokinetic parameters were accomplished. RESULTS After multiple administration, the Gegen Qinlian Decoction+pioglitazone group demonstrated significantly higher AUC, MRT0~t , Cmax, Tmax (P <0.05, P <0.01) and lower CLz/F (P<0.01) than the pioglitazone group, together with obviously increased MRT0~t , t1/2, obviously decreased CLz/F, and 1.81, 2.13 times increase in AUC0~t , Cmax, respectively. CONCLUSION The multiple administration of Gegen Qinlian Decoction can improve the overall exposure level of pioglitazone in rats as compared with single administration.