Bioavailability Evaluation of Sustained-Release Metformin Formulation After Single and Multiple Oral Dosing in Healthy Volunteers / 复旦学报（医学版）

ABSTRACT

Purpose To evaluate the relative bioavailability of a domestic sustained-release metformin tablets (SRM) compared against an immediate-release metformin tablets (IRM) using a multiple-dose,two-way crossover design after a single-dose study. Methods Eighteen healthy adult male volunteers,aged 18 to 22 years (mean,20 years),weighing 55 to 76 kg (mean,64 kg) and with height ranging from 166 to 180 cm (mean,173 cm),and blood glucose levels from 4.0 to 5.9 mmol/L (mean,4.3 mmol/L) participated in the study.The concentrations of metformin in plasma were determined using a ion-pair liquid chromatographic method. Results In single-dose study,the mean residence time (MRT),Tmax,and apparent elimination half-life (T1/2) for SRM were significantly longer and Cmax significantly lower than the corresponding values determined for IRM.The similar results were also demonstrated in multiple-dose study.The mean values of the relative bioavaibility of SRM compared with IRM in two administration ways were (85.95±0.97)% and (86.44±7.88)%,respectively.The single-dose and multiple-dose administration of the 90% confidence interval for the ratio of the logarithmic transformed AUC values of SRM over those of IRM were calculated to lie between 0.83 and 0.88,0.83 and 0.89,respectively,being within the acceptable bioequivalence limit of 0.80～1.25. Conclusion SRM was of the characteristic of sustained-release pharmacokinetics.The relative bioavailability for single dosing was similar to that of multiple dosing,and both of the administration ways demonstrated bioequivalence in absorption between SRM and IRM.