Bioequivalence study of nabumetone tablets in man

A nabumetone tablet in development (Nabuton^R) was tested for its bioequivalence to the reference tablet (Uniton^R). Seventeen healthy Korean male subjects participated in this study. Each subject received a 1-g dose of nabumetone (2 tablets each) in an unbalanced, randomized, two-way crossover investigation. Serum concentrations of 6-methoxy-2-naphthylacetic acid (6-MNA), a major metabolite of nabumetone, were measured over 120 hr interval by a high-performance liquid chromatography. The maximum serum concentration (C_max) and time to reach the maximum concentration (T_max) were read directly, but area under the serum concentration time curve from time 0 to 120 hr (AUC) and mean residence time (MRT) of 6-MNA were calculated from the serum 6-MNA concentration-time curves. The serum curves showed multiple peaks of 6-MNA in most subjects, and the C_max and T_max were read from the highest serum peaks. Calculated bioavailability parameters for test and reference tablets were 1498.6:1377.9 μg·hr/ml for AUC; 25.2:23.1 μg/ml for C_max; 11.8:16.4 hr for T_max and 42.6:43.8 hr for MRT, respectively. The paired t-test revealed no significant differences in all the parameters between the two tablets. Analysis of variance (ANOVA) revealed no significant differences between groups and formulations in all the parameters (C_max, T_max, AUC and MRT) indicating the crossover design of the experiment was properly performed. But significant differences (p<0.05) between subject/groups and periods were found for all the parameters indicating substantial intersubject and interperiodic variations for these parameters.