Relative bioavailability and bioequivalence of metforphin hydrochloride extended-released and immediate-released tablets in healthy Chinese volunteers

Abstract

The aim of the present study was to investigate the relative bioavailability and bioequivalence of a new tablet formulation of metformin hydrochloride with reference to a standard product in healthy Chinese adult male volunteers. Two randomized, comparative, two-way crossover studies were therefore conducted. In study 1, which was a single-dose study, 20 subjects received 1000 mg metformin hydrochloride test product extended-release (MXR) tablets followed by the same amount of metformin hydrochloride reference product immediate-release (MIR) tablets with a 7-day washout period between the two doses. In study 2, which was a multiple-dose study, 22 subjects received MXR 1000 mg/d for 9 consecutive days followed by MIR 1000 mg/d with a 14-day washout period between the doses of the test and reference product. The serum metformin concentrations were monitored using a selective and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. The pharmacokinetic parameters were calculated using a 3P97 program. Analysis of variance (ANOVA) of the half-life of the absorption phase (t(1/2ka)), the half-life of the elimination phase (t(1/2ke)) and the mean retention time (MRT) and the Wilcoxon Signed Rank test of T(max) for the two preparations were significantly different. A significant difference was found in the ANOVA for C(max) in the single-dose study, while this was not the case in the multiple-dose study. Two one-sided t-tests showed that there were no significant differences in the area under the concentration-time curve (AUC) values between the two formulations. The present study indicates that the test preparation was bioequivalent to the reference preparation when both MXR and MIR were investigated in healthy Chinese adult male volunteers. And on the basis of the mean AUC(0-t), AUC(0-infinity) and AUC(ss), the relative bioavailability of the MXR was found to be 107.80%, 111.89% and 110.61% respectively compared with MIR.