Bioequivalence of amoxicillin and clavulanic acid tablet

Abstract

The bioequivalence of two brands of 500/125 mg amoxicillin/clavulanic acid film coated tablet were evaluated. In vitro studies indicated that both brands met the general requirements of the United States Pharmacopoeia 25 for content of active ingredients and uniformity of dosage units. Dissolution profile studies revealed that the curves of local product were similar to those of innovator's product. Comparative bioavailability of the local product relative to innovator's product was conducted in 18 healthy Thai male volunteers using an oral single dose of 500/125 mg tablets in a two way crossover design. Blood samples were collected at appropriate time interval. Plasma amoxicillin and clavulanic acid concentrations were determined by high performance liquid chromatography. Individual plasma amoxicillin and clavulanic acid concentration-time profile was analyzed for relevant pharmacokinetic parameters. Data analysis revealed that there were no statistically significant differences (p>0.05) in the corresponding logarithmically transformed pharmacokinetic parameters (AUC and C[subscript]max values) between the local and innovator's products for both amoxicillin and clavulanic acid. The 90% confidence interval for the ratios of individual parameter based on log-transformed data of amoxicillin and clavulanic acid of local product to that of innovator's product were within 80-125% except only that of the parameter C[subscript]max value for clavulanic acid which was found to be 80-126%. This was expected because of the variable nature of clavulanic acid absorption and an inherent variability of C[subscript]max. The 90% confidence interval for the C[subscript]max ratio of such drug was recommended to be 75-133%. Thus, it could be concluded that both products were bioequivalent in terms of both the rate and the extent of drug absorption into systemic circulation.