Bioequivalence and Pharmacokinetics of Metformin Hydrochloride 1000 mg Tablet Extended Formulation in Healthy Indian Male Volunteers

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DOI: 10.4103/2231-4040.197331

This study was to compare the bioavailability and pharmacokinetic properties of test product of Metformin hydrochloride extended release formulation of 1000 mg tablet with reference product of Metformin Hydrochloride (Glucophage®) extended release formulation of 1000 mg in Indian healthy male volunteers. Study design is an open-label, randomized, 2-treatment, single-dose, crossover, bioavailability study to compare test product with reference product in 24 healthy human male volunteers under fed condition. A single oral dose of 1000?mg Metformin (XR) extended release test product, with reference product Metformin Hydrochloride (Glycophage®) extended release was administered as per computer generated randomization schedule during 2 period of the study having 7 days of washout period. A liquid Chromatography mass spectroscopy method was developed and validated as per FDA guideline requirements using Atenolol as an internal standard for the determination of Metformin in human plasma. A non-compartmental pharmacokinetic method was employed to determine the pharmacokinetic parameters (Cmax, Tmax, AUC0-t , AUC0-8 and t½) of Metformin using Kinetica (version 4.4.1) software. Cmax, AUC0-t and AUC0-8 were used to test for bioequivalence after log transformation of Metformin plasma concentration data. The required Bioequivalence acceptance criteria as per regulatory is 90% CI for bioequivalence study and the range is 0.80 to 1.25. The 90% confidence intervals for log transformed data for Cmax, AUC0-t and AUC0-8 for test A vs. reference were 83.18-.95.64, 88.06-104.99 and 94.76-121.59 respectively.

Keywords: Metformin, Bioequivalence, Pharmacokinetics, LC-MS/MS