Pharmacokinetic bioequivalence and safety assessment of two metformin hydrochloride tablet formulations using a phase I, randomized, open, two-period, two cross-over, single-dose, fed study in healthy Chinese adult subjects.

Abstract

To assess the bioequivalence and safety of generic metformin hydrochloride (test preparation) and glucophage (reference preparation) in healthy Chinese subjects. A bioequivalence and safety assessment of two formulations of metformin (850 mg) using a randomized, open, two-period, two cross-over, single-dose, fed trial in 36 healthy Chinese adult subjects was performed at our center from March 22, 2018, to April 9, 2018. Bioequivalence was determined as two-sided 90% confidence intervals (CI) of the test-to-reference ratio of area under the curve (AUC) and peak concentration (Cmax) for each constituent within 80.00-125.00%. SAS 9.4 software was employed for the statistical analysis. One subject was excluded from the trial. The 90% CIs (95.36-101.43% for AUC0→t, 95.65-101.66% for AUC0→∞; 94.43-101.74% for Cmax) of test/reference preparation for these pharmacokinetic parameters were within the range of 80.00-125.00%. No severe adverse events were observed during this trial. The two preparations were safe and well-tolerated. It was concluded that generic metformin was bioequivalent and as safe as glucophage under fed conditions in healthy Chinese subjects.