盐酸二甲双胍缓释片的生物等效性评价

 目的对国产两种盐酸二甲双胍缓释片制剂进行生物等效性评价。方法单剂量(1 000 mg)、多剂量(1 000 mg·d^-1×7d)试验各选20例受试者,受试者随机分组、自身对照口服药物,采用反相HPLC测定血浆中盐酸二甲双胍的浓度,并计算相关药动学参数判定两制剂是否生物等效。结果单剂量时,受试制剂与参比制剂主要药动学参数ρ_max分别为(2.329±0.486)及(2.308±0.502)mg·L^-1;t_max分别为(3.700±0.571)及(3.600±0.940)h;t_1/2分别为(7.484±2.612)及(7.724±2.799)h;AUC_0～t分别为(13.387±3.394)及(13.589±2.917)mg·h·L^-1;AUC_0～∞分别为(18.575±3.841)及(19.069±3.792)mg·h·L^-1;受试制剂相对于参比制剂的生物利用度F为(98.10±8.90)%。多剂量时,受试制剂与参比制剂主要药动学参数ρ_max分别为(1.876±0.545)及(2.111±0.630)mg·L^-1;ρ_min分别为(0.212±0.047)及(0.227±0.054)mg·L^-1;t_max分别为(4.100±0.912)及(3.750±0.716)h;t_1/2分别为(11.477±3.851)及(13.529±4.067)h;AUC_ss分别为(15.137±2.749)及(15.855±3.322)mg·h·L^-1;ρ_av分别为(0.631±0.114)及(0.661±0.138)mg·L^-1;DF分别为(2.609±0.644)%及(2.812±0.645)%;受试制剂相对于参比制剂的生物利用度F为(98.00±22.7)%。结论统计分析结果显示,受试制剂与参比制剂生物等效。

Studies on Bioequivalence of Metformin Hydrochloride Sustained Release Tablets

OBJECTIVE To study the bioequivalence of metformin hydrochloride tablets in healthy volunteers.METHODS A single oral dose(1 000 mg) and multiple oral doses(1 000 mg·d^-1×7 d) of reference or test metformin hydrochloride preparations were given to 20 healthy male volunteers according to an open randomized crossover study.The plasma concentrations of metformin hydrochloride were determined by RP-HPLC method.The pharmacokinetic parameters and bioavailability of test preparation were compared with reference preparation.RESULTS The main pharmacokinetic parameters of the test preparation and the reference preparation were as follows,single dose(SD): ρ_max(2.329±0.486) and(2.308±0.502) mg·L^-1;t_max(3.700±0.571) and(3.600±0.940)h;t_1/2(7.484±2.612) and(7.724±2.799)h;AUC_0～t(13.387±3.394) and(13.589±2.917) mg·h·L^-1;AUC_0～∞(18.575±3.841) and(19.069±3.792) mg·h·L^-1.The relative bioavailability of the test to reference preparation was(98.10±8.90)%.Multiple doses(MD): ρ_max(1.876±0.545) and(2.111±0.630) mg·L^-1;ρ_min(0.212±0.047) and(0.227±0.054)mg·L^-1;t_max(4.100±0.912) and(3.750±0.716)h;t_1/2((11.477±3.851))and(13.529±4.067) h;AUC_ss(15.137±2.749) and(15.855±3.322) mg·h·L^-1;ρ_av(0.631±0.114) and((0.661±0.138)) mg·L^-1;DF(2.609±0.644)% and(2.812±0.645)%,respectively.The relative bioavailability of test to reference preparation was(98.00±22.7)%.CONCLUSION The results of statistic analysis show that the reference preparation and the test preparation are bioequivalent.