Comparison of Bioavailability and Pharmacokinetic of Two Formulations of Metformin 850 mg Tablets in Healthy Albanian Volunteers

Abstract

Aim: The aim of this study was to compare the bioavailability and pharmacokinetics of two formulations of metformin 850 mg tablets: GLUCOPHAGE^® from Merck Santè laboratories (reference product) and METFORMINE from Profarma (test product) in healthy Albanian volunteers.

Methods: An open label, randomized, two-period, two-way crossover study was performed in twenty healthy volunteers for a single 850 mg dose of metformin tablets. Pharmacokinetic parameters such as maximum plasma concentration (Cmax), the area under the curve limited to a specific time (AUC_0-14h), the area under the curve to infinite time (AUC_0-\(\infty\)), and the time to reach the maximum plasma concentration (Tmax) were determined. The formulations were considered bioequivalent if the logarithmic mean ratios of ln-transformed Cmax and AUC_0-\(\infty\) values were within the equivalence range of 80%-125%. 

Results: Two Way ANOVA analysis of the ln-transformed C_max and AUC_0-\(\infty\) indicated that none of the effects examined (formulation, period, within and between-subject variances and carry over) was statistically significant. The bioequivalence study results showed 90% confidence of intervals (90 % CI) for pharmacokinetic parameters like Cmax (91.8-115.6 %); AUC0-14 (90.4-109.2 %) AUC0_-\(\infty\) (90.1-109.1%) and which were within the range of 0.80-1.25. A p value of less than 0.05 was considered statistically significant.

Conclusion: The product METFORMINE (produced by Profarma Sh.a) is bioequivalent and, therefore, fully interchangeable regarding AUC_0-\(\infty\) and Cmax when compared with the reference product (GLUCOPHAGE®).