Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers

In the present study two different formulations containing 50 mg itopride HCl (N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide HCl, CAS 122898- 67-3) were compared in 28 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, crossover design in 28 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 24 h. The serumconcentrations of itopride HCl were determined using a specific and sensitive HPLC method with fluorescence detection. The detection limit of itopride HCl was 5 ng/ml and no endogenous compounds were found to interfere with analysis. The mean AUC _0→24h, AUC_0→∞, C_max, T _max and T_1/2 were 865.28 ng · h/ml, 873.04 ng · h/ml, 303.72 ng/ml, 0.75 h, and 2.95 h, respectively, for the test formulations, and 833.00 ng · h/ml, 830.97 ng · h/ml, 268.01 ng/ml, 0.78 h, and 2.83 h, respectively, for the reference formulation. Both primary target parameters AUC_0→∞ and C_max were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of AUC_0→∞ and C_max were 100.57%-109.56% and 105.46%-121.18%, respectively, and were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of itopride HCl are considered to be bioequivalent.