Bioavalaibility and pharmacokinetic comparison of two formulations of metformin 850 mg tablets in healthy Colombian volunteers

Abstract

urpose: The aim of this study was to compare the bioavailability of two formulations of metformin 850 mg tablets: Glucophage® from Merck Santè laboratories (reference product) and Metformin from Winthrop Pharmaceuticals de Colombia SA (test product) in healthy Colombian volunteers.
Methods: A random, double blind, two-period, two-week wash out period, crossover study was performed in 24 healthy male and female volunteers for a single 850-mg dose of metformin tablets administrated with 240 ml of water after 12 hours of fasting. Once the drug was administrated, blood samples were collected before and within 24 hour, and plasma metformin concentration was determined by using a validated HPLC method. Pharmacokinetic parameters such as C_max, AUC_0-96h, AUC_0-∞, and T_max were determined. The formulations were considered bioequivalent if the logarithmic mean ratios of ln-transformed C_max and AUC_0-∞ values were within the equivalence range of 80%-125%.
Results: ANOVA analysis of the ln-transformed C_max and AUC_0-∞ indicated that none of the effects examined (formulation, period, within and between-subjet variances and carry over) was statistically significant. The mean (±SD) of C_max 1217.38 (± 251.72) ng/ml vs. 1305.25 (± 301.06) ng/ml, AUC_0-96h 1363.49 (± 315.51) ng.h/ml vs. 1584.82 (± 368.75) ng.h/ml, AUC_0-∞, 7155.75 (± 1440.74) ng.h/ml vs. 7777.08 (± 1896.49) ng.h/ml, and T_max 2.57 (± 0.93) h vs. 2.22 (± 0.94) h were obtained with test and reference formulations, respectively. These pharmacokinetic parameters presented differences with the results from other published papers. The 90% confidence interval of the logarithmic ratio of AUC_0-∞ and C_max was within the range of 80-125%.
Conclusions: In this study in healthy Colombian volunteers, a single 850-mg dose of metformin tablet test formulation met the criteria for bioequivalence to the reference formulation based on pharmacokinetic parameters AUC_0-∞ and C_max.

Authors

• Gloria Holguín
• Fanny Cuesta
• Rosendo Archbold
• Margarita Restrepo
• Sergio Parra
• Lina Peña
• Blanca Montoya
• Juan Carlos Ríos
• Victoria Eugenia Toro
• Adriana Ruiz