DETERMINATION OF BIOEQUIVALENCE OF METFORMIN TABLETS USING URINARY EXCRETION DATA

Abstract

The aim of the present study was to assess the bioequivalence of two metformin tablet formulations available in the Albanian market (product R as reference formulation and product T as test formulation). The bioequivalence study was performed in eighteen healthy volunteers in a two - treatment, open, crossover design. Single oral dose (tablet containing 850 mg of metformin) of each product was administered with one week of washout period. Urinary concentrations of metformin were measured by high-performance liquid chromatography (HPLC) method and pharmacokinetics parameters were estimated by urinary excretion data. The bioequivalence was determined by the following parameters: the cumulative amount of metformin excreted in the urine, the total amount of metformin excreted in the urine and the maximum urinary excretion rate of metformin. Various pharmacokinetic parameters like peak excretion rate [(dDU/dt)_max], time for peak excretion rate (t_max), cumulative amount (D_cum0-24), total amount of drug recovered from urine (D_cum0-∞),  elimination half-life (t_1/2), and terminal elimination rate constant (kel), were calculated for both the formulations.
The average cumulative amounts of metformin excreted in urine after administration of Formulation R and Formulation T were found to be 346.3 mg (40.74% of dose) and 358.7 mg (42.2% of dose), respectively. The urinary excretion profiles of metformin up to 24 h for both the formulations were found to be similar. Statistical comparison (90% confidence intervals of ratio) of pharmacokinetic parameters were in compliance with the international standards, indicating that products R and T can be considered bioequivalents and therefore interchangeable.

Keywords

• Metformin,urinary excretion,bioequivalence study

References

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