Comparative Bioequivalence Studies of Two Metformin Extended- Release Formulations in Healthy Thai Volunteers

Abstract

Metformin is a first-line treatment for type 2 diabetic mellitus commonly used as a monotherapy or in a combination with other antidiabetic drugs. To control blood glucose levels, patients should be able to access to the treatment continuously. Thus, the Government Pharmaceutical Organization (GPO) had developed a generic metformin extended-release formulation as a low-cost alternative for patients and physicians. Two bioequivalence studies were conducted under fasting and fed conditions to compare the rate and extent of absorption between the test (Metformin XR 1000 mg) and reference (Glucophage XR 1000 mg) formulations. The study design for both studies was comparative randomized, open-label, single-dose, two-way crossover. Twenty-four subjects and fourteen eligible subjects were enrolled in the single-dose fasting and fed studies, respectively. Plasma concentrations of metformin were determined using a validated liquid chromatography tandem mass spectrometry method. The primary pharmacokinetics parameters including AUC 0-tlast , AUC 0−∞ and C max were statistically compared. The 90% confidence intervals of the geometric least squares mean ratio of log-transformed AUC 0-tlast , AUC 0−∞ and C max between the formulations were within 80.00-125.00% of bioequivalence criteria for both fasting and fed studies. The pharmacokinetic parameters following oral administration under fasting and fed conditions were comparable suggesting insignificant food effect on the absorption. The safety of metformin extended-release formulations was evaluated in healthy Thai subject. The test and reference products were well tolerated by the study subjects and no serious adverse events were reported in both studies. Based on the statistical indices, it was concluded that two metformin extended-release formulations were bioequivalent.