盐酸二甲双胍片人体药代动力学和生物等效性研究

Study on pharmacokinetics and bioequivalence of Metformin Hydrochloride Tablet in Human

目的进行盐酸二甲双胍片在健康人体的药代动力学和生物等效性研究.方法采用双交叉试验设计,18名健康受试者随机分为两组,单次口服试验制剂或参比制剂盐酸二甲双胍1000mg后,用高效液相色谱法测定血浆中二甲双胍浓度,血药浓度-时间数据经DAS1.0软件计算得药代动力学参数,并评价两种制剂的生物等效性.结果试验制剂和参比制剂盐酸二甲双胍片的药代动力学参数分别为Cmax(2.00±0.37)和(1.96±0.42)μg·mL-1,AUC0～24(10.71±1.42)和(10.62±1.32)μg·mL-1·h,AUC0～∞(12.00±1.51)和(11.94±1.46)μg·mL-1·h,t12(7.97±0.71)和(8.10±0.60)h,Tmax(1.89±0.21)和(1.89±0.21)h,试验制剂盐酸二甲双胍片相对生物利用度为(100.97±7.73)%.结论试验制剂和参比制剂盐酸二甲双胍片主要药代动力学参数Cmax、AUC0～24、AUC0～∞及t21经统计学分析均无显著性差异,提示试验制剂与参比制剂盐酸二甲双胍片为生物等效制剂.

OBJECTIVE To study the pharmacokinetics and bioequivalence of Metformin Hydrochloride Tablet in human. METHODS In a randomized and cross-over study, 18 healthy volunteers were divided into two groups and orally given 1000mg Metformin Hydroehloride Tablet （test or reference）. A sensitive and rapid HPLC method was developed to determine the metformin plasma concentration. The plasma concentration-time curves and the bioequivalence of reference and test preparation were analyzed by DAS1.0 software. RESULTS The main pharmacokinetic parameters were as follows,Cmax（2.00±0. 37） and （1.96±0. 42）ug · mL^-1 , AUC0-24 （10. 71±1.42） and （10. 62±1.32）ug · mL^-1 · h,AUC0-∞ （12.00±1. 51） and （11.94 ±1. 46）ug· mL^-1 · h, t1/2 （7.97±0. 71） and （8. 10±0.60）h,Tmax（1.89±0. 21） and （1.89±0. 21）h. The relative bioavailability of Metformin Hydrochloride Tablet test was （100. 97±7.73）%. CONCLUSION The main pharmacokinetic parameters （Cmax , AUC0-24 , AUC0-∞ （ and t1/2 ） of metformin hydrochloride tablet test and reference were no statistically significant differences. The reference and test preparation were bioequivalent.