Abstract
Abstract
This study was undertaken to compare the bioavailability and pharmacokinetic properties of 3 marketed product of metformin (CAS 1115-70-4) extended/sustained release formulation in Indian male volunteers. Study was designed as an open-label, randomized, 3-treatment, single-dose, crossover, bioavailability study comparing 3 marketed brands of 500 mg metformin extended/sustained release tablets in 18 healthy human male volunteers under fed condition. A single oral dose of 500 mg metformin sustained release products, test A (Glycomet SR), test B (Bigomet SR) and extended release reference product was administered as per computer generated randomization schedule during 3 period of the study having 7 days of washout period. A liquid Chromatography mass spectroscopy method for the determination of metformin in human plasma was developed and validated using metformin-D6 as an internal standard. A noncompartment pharmacokinetic method was employed to determine the pharmacokinetic parameters (C
max
, T
max,
AUC
0–t,
AUC
0–∞
and t½) of metformin using WinNonlin-Node 4.0 software. C
max
, AUC
0–t
and AUC
0–∞
were used to test for bioequivalence after log transformation of plasma data. The predetermined regulatory range of 90% CI for bioequivalence was 0.80 to 1.25. The 90% confidence intervals for log transformed data for C
max
, AUC
0–t
and AUC
0–∞
for test A vs. reference were 82.11–98.91, 86.29–102.17 and 86.34–102.59 respectively whereas for test B vs. reference were 104.39–125.76, 94.78–112.22 and 92.85–110.33 respectively. The results of this study suggest that the test A was bioequivalent to reference product, whereas test B was not as per regulatory defined criteria.