The aim of this study was to examine the bioequivalence of generic MESALAMINE 400 mg tablets (T) manufactured by APL Research Centre Pv.T., Ltd, India and a reference (R) manufactured by SUN Pharma Ltd., India (Mesacol®) in healthy volunteers. Thirty-four subjects (+4 reserve) were randomly selected. Each subject was randomly allocated to one of two treatment sequences (TR or RT). After an overnight fasting period of 10 h, the subjects were administered either the test or the reference formulation as per the randomization schedule. The two treatments were separated by a 7-day washout period. Twenty nine blood samples (4 mL each) were drawn at predose (0 h), 2, 3, 4, 5, 6, 7, 8,9,10,11,12.5,14,16, 18, 20,22, 24, 26, 28, 30, 32, 36, 40, 44, 48, 60, 72, 84 and 96 h post-dose. Concentrations of mesalamine in plasma were analyzed by a validated LC-MS/MS method, with LLOQ 2 ng/mL for Mesalamine and 10 ng/mL for N-Acetyl mesalamine . The pharmacokinetic parameters, Cmax, AUC0-tlast, AUC0-∞, Tmax, t1/2, and kel, were calculated using a non-compartment model. The log transformed geometric mean ratios (GMR) of Cmax, AUC0-tlast and AUC0-∞ were tested for bioequivalence using a 2-way ANOVA. Thirty-eight subjects were enrolled and completed the study. The mean (test and reference) were: Cmax (849.41 and 719.92 ng/mL); AUC0-tlast (8711.94 and 7352.55 ng.h/mL); AUC0-∞ (8728.24 and 7367.14ng.h/mL); and t1/2 (9.40 and 9.41h) for mesalamine and , Cmax (1170.33 and 1118.30ng/mL); AUC0-tlast (30021.90 and 26136.86ng.h/mL); AUC0-∞ (30694.39 and 26429.16ng.h/mL); and t1/2 (15.20 and 12.54h) for N-Acetyl mesalamine respectively. The respective median Tmax were 6 and 7 h for mesalamine and 9 h for N-Acetyl mesalamine respectively. The GMR (90% CI) of Cmax, AUC0-tlast, and AUC0-∞ were within the bioequivalence limit of 80-125%. Both formulations were well tolerated. The study demonstrated the bioequivalence of the two formulations of mesalamine 400 mg.
