title: Bioequivalence and pharmacokinetic comparison of 3 metformin extended/sustained release tablets in healthy Indian male volunteers.
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.
authors.affiliation: Faculty of Pharmaceutical Medicine, Jamia Hamdard, New Delhi, India.
authors.forename: L S
authors.initials: LS
authors.lastname: Batolar
authors.forename: M
authors.initials: M
authors.lastname: Iqbal
authors.forename: T
authors.initials: T
authors.lastname: Monif
authors.forename: A
authors.initials: A
authors.lastname: Khuroo
authors.forename: P L
authors.initials: PL
authors.lastname: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics*; D008875:Middle Aged; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D013607:Tablets; D008687:Metformin