二甲双胍与二甲双胍-牛磺酸复方制剂在Beagle犬体内的药物动力学考察

Pharmacokinetics of single metformin hydrochloride and compound metformin-taurine capsules in Beagle dogs

目的比较单组分二甲双胍与二甲双胍复方制剂的药物动力学差异,为复方制剂的组方及临床应用提供参考。方法Beagle犬口服给予盐酸二甲双胍胶囊(10 mg.kg-1)和二甲双胍-牛磺酸复方制剂胶囊(等同于盐酸二甲双胍10 mg.kg-1),RP-HPLC法测定其血药质量浓度,拟合药物动力学曲线,计算药物动力学主要参数。结果单一制剂与复方制剂的二甲双胍在Beagle犬体内药物动力学都符合二室模型,主要药物动力学参数为AUC0-t(10.29±3.54)、(10.12±2.81)mg.h.L-1,ρmax(2.11±0.46)、(1.73±0.49)mg.L-1,tmax(2.67±0.41)、(2.50±0.45)h。结论单一制剂与复方制剂给药的二甲双胍主要药物动力学参数采用双侧t检验,无显著性差异(P>0.05),提示二甲双胍-牛磺酸复方制剂具有药物动力学理论的可行性。

Objective To study the pharmacokinetic behavior of mefformin and compare the pharmacokinetic difference between single mefformin hydrochloride and compound preparation of metformin-taurine（ m： m = 1： 1 ） in dogs and their mutual influences. Methods Single oral administration of metformin hydrochloride and compound preparations were given to 6 Beagle dogs separately. The concentrations of metformin in serum were determined by RP-HPLC, the interpolated pharmacokinetic curve was drawn and the main pharmacokinetic parameters were calculated. Results The serum drug concentration-time course in dogs was conformed to the two-compartments model after oral administration single of metflrmin hydrochloride and compound preparation of metflrmin hydrochloride-taurine capsules, and main pharmacokinetic parameters were as fop lows：AUC0-t（10. 29 ± 3.54）mg·h·L^-1 and （10.12 ± 2. 81 ）mg·h·L^-1 ,pmax（2. 11 ± 0. 46）mg·L^-1 and （ 1.73 ± 0. 49 ） mg·L^-1, tmax （2. 67 ± 0. 41 ） h and （ 2. 50 ± 0. 45 ） h, respectively. Conclusions Single oral administration of metformin and compound preparation of metformin-taurine to Beagle dogs appears to have no mutual influence in pharmacokinetic studies. It is theoretically feasible to develop new preparation with metformin hydrochloride and taurine.