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 (Cmax, Tmax, AUC0–t, AUC0–∞ and t½) of metformin using WinNonlin-Node 4.0 software. Cmax, AUC0–t and AUC0–∞ 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 Cmax, AUC0–t and AUC0–∞ 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.
Key words
metformin - extended/sustained release - pharmacokinetics - bioequivalence
