Bioequivalence study of a generic Risperidone (Iperdal ) in healthy Thai male volunteers

The objective of this study was to compare the rate and extent of absorption of a generic risperidone (Iperdal ) with a reference formulation (Risperdal ) when given orally. The study was an open label, randomized, two-period, two-sequence,single dose cross-over design with a 2 weeks washout period in 16 healthy Thai male volunteers. Single oral dose of two 2-mg tablets of risperidone were administered and serial blood samples were collected from the antecubital vein before and at0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 and 48 hours post dose. Risperidone plasma concentrations were assayed using a validated High Performance Liquid Chromatographic (HPLC)-UV method modified from Avenosoet al. (2000). Pharamcokinetic parameters i.e. Cmax, AUC0à48 and Tmax were analyzed by noncompartment analysis. Variations of the data were analyzed by Two Way Analysis of Variance (ANOVA). Statistics were tested as stated in USP 28 guidelinefor bioequivalence study. The maximum concentration (Cmax, ng/ml) of risperidone for the innovator and the generic product were 31.11±17.24 (range 5.64-56.78) and 32.58±19.77 (range 5.29-84.56) ng/ml, respectively. The area under theplasma concentration-time curve (AUC0 48) of the innovator and the generic product were 160.64±152.89 (range 18.57- 550.32) and 144.03±127.37 (range 16.27-456.0) ng.hr/ml, respectively. The time to maximum concentration (Tmax) of theinnovator and the generic product were 0.97±0.41(range 0.5-2) and 1.02±0.32 (range 0.5-1.5) hr, respectively. The 90% confidence interval of the ratio of the ln-transformed of Cmax and AUC0à48 of both preparations were 89.39-112.99% and80.02-107.28% respectively which were within the acceptance range of 80.00-125.00%. Therefore, it can be concluded that both preparations used in this study are bioequivalent in terms of both the rate and extent of absorption.