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目的 以一种进口速释片 (IRM)为对照 ,通过单剂量和多剂量口服给药后 ,评价国产二甲双胍缓释片(SRM)的相对生物利用度。方法 选择 1 8名健康男性受试者 ,年龄 1 8～ 2 2岁 ,体重 5 5～ 76kg ,身高 1 6 6～ 1 80cm ,血糖水平 4 .0～ 5 .9mmol/L。采用离子对色谱法测定血浆中二甲双胍SRM的浓度。结果 与IRM比较 ,单剂量给药后 ,SRM的MRT、tmax和t1 /2 明显延长 ,cmax显著降低。这一结果与多剂量试验一致。单剂量和多剂量试验中 ,SRM的相对生物利用度分别为 (85 .95± 0 .97) %和 (86 .4 4± 7.88) %。对数转换后 ,AUC的 90 %置信区间分别为 0 .83～ 0 .88和 0 .83～ 0 .89,在生物等效的 0 .80～ 1 .2 5范围内。结论 SRM具有缓释动力学特征 ;单剂量给药的相对生物利用度近似于多剂量给药 ;两种给药方式均证明SRM和IRM两制剂生物等效。
OBJECTIVE To evaluate the relative bioavailability of domestic metformin sustained-release tablets (SRM) after oral administration of one fast-acting tablet (IRM) as a control after single and multiple doses of oral administration. Methods A total of 18 healthy male subjects, aged 18 to 22 years old, weighing 55 to 76 kg, height 166 to 180cm and blood glucose level 4.0 to 5.9 mmol / L, were selected. Plasma concentrations of metformin SRM were determined by ion-pair chromatography. Results Compared with IRM, MRM, tmax and t1 / 2 of SRM significantly prolonged and cmax decreased significantly after single-dose administration. This result is consistent with multiple dose trials. The relative bioavailability of SRM was (85.95 ± 0.97)% and (86.4 ± 7.88)%, respectively, in single-dose and multi-dose experiments. After logarithmic conversion, the 90% confidence intervals for AUC ranged from 0.83 to 0.88 and from 0.83 to 0.89, respectively, within a bioequivalent range of 0.80 to 1.25. Conclusions SRM has the characteristics of sustained-release kinetics. The relative bioavailability of single-dose administration is similar to that of multiple-dose administration. Both of the two administration methods prove that SRM and IRM are bioequivalent.