Technological evaluation and equivalence assessment of lorazepam tablets in rabbits

Four different oral lorazepam tablets (Tavor® tablets as reference preparation and three generic tablet formulations, A, B and C) were investigated after administration to 12 rabbits to evaluate their bioequivalence. A single 2 mg/kg dose was administered orally as powder and lorazepam plasma concentrations were determined by a validated HPLC method. Maximum plasma concentrations (Cmax), of 207 ng/ml (reference), 198 ng/ml (A), 166 ng/ml (B) and 169 ng/ml (C) were achieved. Lorazepam appeared in the plasma at 0.66 h (Tmax) for all formulations, probably because the disintegration step was bypassed due to the pulverization of the administered doses. Areas under the plasma concentration-time curves (AUC0-t and AUC0-∞) were determined. The obtained AUC0-t values were 556.57 ng h/ml (reference), 554.70 ng h/ml (A), 493.08 ng h/ml (B), and 487.88 ng h/ml (C). ANOVA results (P ≥ 0.05) and 90% confidence intervals for the mean ratio (T/R) of AUC0-t, AUC0-∞ and Cmax were within the EMEA acceptance range. Pharmacokinetic and statistical results of this study show that the four tested drug products (Tavor®, A, B, C) are to be considered bioequivalent and interchangeable in medical practice.