DETERMINATION OF BIOEQUIVALENCE OF METFORMIN TABLETS USING URINARY EXCRETION DATA

Abstract

The aim of the present study was toassess the bioequivalence of two metformin tablet formulations available in theAlbanian market (product R as reference formulation and product T as testformulation). The bioequivalence study was performed in eighteen healthyvolunteers in a two - treatment, open, crossover design. Single oral dose (tabletcontaining 850 mg of metformin) of each product was administered with one weekof washout period. Urinary concentrations of metformin were measured byhigh-performance liquid chromatography (HPLC) method and pharmacokineticsparameters were estimated by urinary excretion data. The bioequivalence wasdetermined by the following parameters: the cumulative amount of metforminexcreted in the urine, the total amount of metformin excreted in the urine andthe maximum urinary excretion rate of metformin. Various pharmacokinetic parameters like peak excretion rate [(dDU/dt)max],time for peak excretion rate (tmax), cumulative amount (Dcum0-24),total amount of drug recovered from urine (Dcum0-∞),  elimination half-life (t1/2),and terminal elimination rate constant (kel), were calculated for both theformulations.The average cumulative amounts of metformin excreted in urine afteradministration of Formulation R and Formulation T were found to be 346.3mg (40.74% of dose) and 358.7 mg (42.2% of dose), respectively. The urinaryexcretion profiles of metformin up to 24 h for both the formulations were foundto be similar. Statistical comparison (90% confidenceintervals of ratio) of pharmacokinetic parameters were in compliance with the international standards,indicating that products R and T can be considered bioequivalents and thereforeinterchangeable.