Bioequivalence and Pharmacokinetic Evaluation of Two Metformin Hydrochloride Tablets Under Fasting and Fed Conditions in Healthy Chinese Volunteers.

Abstract

Background and objectives: With diabetes prevalence rising and original formulations unable to meet demand, establishing generic equivalence is crucial for treatment accessibility. This study evaluated the bioequivalence of generic metformin hydrochloride (0.25 g) versus the reference drug in Chinese volunteers under fasting and fed conditions.

Methods: In this randomized, open-label, two-period crossover trial, 26 healthy volunteers per group received single doses under fasting and fed conditions. Plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, pharmacokinetic metrics were calculated using the WinNonlin 6.3 software, and bioequivalence was evaluated using SAS 9.4.

Results: Under fasting conditions, the geometric mean ratios (GMRs) between the test and reference groups were 103.12% (C_max), 103.65% (AUC_0-t), and 103.31% (AUC_0-∞), with 90% CIs of 92.64-114.78%, 96.04-111.85%, and 96.00-111.17%, respectively. Fed conditions yielded GMRs of 93.98% (C_max), 97.34% (AUC_0-t), and 96.97% (AUC_0-∞), with 90% CIs of 89.42-98.78%, 92.72-102.18%, and 92.40-101.78%, respectively. All these parameters met bioequivalence criteria (80-125%). Median T_max was delayed under fed conditions (2.125 h vs. 4.000 h), with consistent food effects (reduced C_max and AUC) and safety profiles between formulations.

Conclusion: These results demonstrate that the generic metformin formulation is bioequivalent to the innovative product and well tolerated in Chinese healthy volunteers under both fasting and fed conditions.