Comparative Bioavailability and Pharmacokinetics of Two Trazodone HCI Products

Abstract

The purpose of this study was to determine the pharmacokinetics and comparative bioavailability of trazodone HCl tablets manufactured by two different drug companies. The pharmacokinetics (PK) and comparative bioavailability of the two formulations of trazodone HCl tablets were investigated in 23 healthy volunteers in an open randomized cross-over trial after a single oral dose of 100 me. The concentration of trazodone in plasma was determined by a modified high performance liquid chromatographic method (HPLC) with ultraviolet (UV) detection. Eleven subjects completed the study and one subject dropped out due to severe dizziness. Intra-day and inter-day coefficients of variation (CV) were within 9%.The detection limit was 0.06me/L for plasma. The average bioavailability and pharmacokinetic parameters of the two trazodone HCl products were as follows: peak plasma concentration(Cmax): 0.99:t 0.23 mg/L, 0.93 t 0.25 mg/L; time to peak plasma concentration (Tmax): 2.00 t 1.34 hours, 1.41±1.07 hours; plasma half-life (T1/2): 5.67±2.09 hours, 5.40:t 1.95 hours; Area under the plasma concentra-tion-time curve (AUCo→∞): 7.60±2.49 mg-hr/L, 7.01 ±2.30 mg-hr/L; AUCO→36: 6.82±2.52 mg-hr/L, 6.28±2.39 mg-hr/L; area under the plasma moment-time curve (AUMC): 65.71±34.08 g-hr2/L, 60.78:t 28.3 t mg-hr2/L; mean residence time (MRT): 8.29±2. 18 hours, 8.30±1.77 hours for Mesyrel@ tablets (Lotus Pharmaceutical Co.) and Desyrel@ tablets (Mead Johnson Pharma cortical Division, U.S.A.), respectively. No statistically significant differences were observed for 0, 05). The narrow Ci90% values, the high power values, and the results of two one-sided t-tests also show that the two products are bioequivalent. The PK parameters obtained in this study are similar to those reported previously.