盐酸二甲双胍缓释片的药代动力学及相对生物利用度研究

目的研究盐酸二甲双胍缓释片的药代动力学和相对生物利用度。方法采用HPLC法测定20名健康男性志愿者,随机自身交叉单剂量和多剂量口服盐酸二甲双胍缓释片1000mg后的血药浓度,得出相应的药时曲线,计算各药代参数和相对生物利用度。结果20名健康志愿者单次口服盐酸二甲双胍缓释片1000mg的主要药代动力学参数分别为:t1/2(5.79±3.05)h和(6.87±4.59)h;Cmax(1185.75±318.92)ng.mL-1和(1232.19±321.91)ng.mL-1;tmax(3.80±1.01)h和(4.05±0.83)h;MRT(8.96±3.00)h和(10.32±4.70)h;AUC0-24h(8724.58±3203.33)ng.h.mL-1和(8642.79±2512.83)ng.h.mL-1;AUC0-∞(9631.89±3796.98)ng.h.mL-1和(9977.48±3317.60)ng.h.mL-1。多次口服盐酸二甲双胍缓释片(1000mg×7d)的主要药代动力学参数分别为:Cmax(1300.91±250.39)ng.mL-1和(1355.00±321.86)ng.mL-1;Cmin(90.59±20.97)ng.mL-1和(87.93±23.73)ng.mL-1;tmax(4.15±1.14)h和(4.60±0.82)h;AUCss(11120.50±2708.06)ng.h.mL-1和(11570.97±3513.51)ng.h.mL-1;DF(2.73±0.57)%和(2.76±0.62)%(DF为血药浓度的波动度)。两种制剂的药动学参数无显著性差异(P>0.05),受试制剂的相对生物利用度(F)为(98.40±15.50)%。结论两种制剂具有生物等效性。

Study of pharmacokinetics and relative bioavailability of metformin hydrochloride sustained-release tablets

Objective To study the relative bioavailability and the phamacokinetics of metformin hydrochloride sustained-release tablets.Method A single and multiple oral administration 1000 mg of metformin sustained-release tablets were given in 20 healthy male volunteers divided into two groups according to randomized crossover design.Metformin concentrations in plasma were determined by HPLC.The pharmacokinetic parameters and relative bioavailability of tested tablets were calculated and compared with that of reference tablets.Result After a single oral administration 1000 mg of sustained-release tablets and reference tablets,the obtained pharmacokinetic parameters were as follows:t1/2 were(5.79±3.05) h and(6.87±4.59) h;Cmax were(1 185.75±318.92) ng·mL-1 and(1 232.19±321.91) ng·mL-1;tmax were(3.80±1.01) h and(4.05±0.83) h;MRT were(8.96±3.00) h and(10.32±4.70) h;AUC0-24 h were(8 724.58±3 203.33) ng·h·mL-1and(8 642.79±2 512.83) ng·h·mL-1 ;AUC0-∞ were(9 631.89±3 796.98) ng·h·mL-1 and(9 977.48±3 317.60) ng·h·mL-1,respectively.After multiple oral administration(1 000 mg ×7 d),the pharmacokinetics parameters were as follows:Cmax were(1 300.91±250.39) ng·mL-1 and(1 355.00±321.86) ng·mL-1;Cmin were(90.59±20.97) ng·mL-1 and(87.93±23.73) ng·mL-1;tmax were(4.15±1.14) h and(4.60±0.82) h ;AUCss were(11 120.50±2 708.06) ng·h·mL-1 and(11 570.97±3 513.51) ng·h·mL-1;DF were(2.73±0.57) % and(2.76±0.62)%,respectively.The relative bioavailability of tested tablets was(98.40±15.50) %.No significant differences were found among the main pharmacokinetic parameters.Conclusion The two preparations presented bioequivalent.