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 (AUC(0-t) and AUC(0-infinity)) were determined. The obtained AUC(0-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 > or = 0.05) and 90% confidence intervals for the mean ratio (T/R) of AUC(0-t), AUC(0-infinity), 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.
Ventura
C A
CA
Dipartimento Farmaco-Chimico, Università di Messina, Italy.
Giannone
I
I
Musumeci
T
T
Pignatello
R
R
Puglisi
G
G
D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D005260:Female; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008140:Lorazepam / Q000008:administration & dosage*; D011817:Rabbits; D012995:Solubility; D013607:Tablets; D013810:Therapeutic Equivalency
D006993:Hypnotics and Sedatives; D013607:Tablets; D008140:Lorazepam