Werawath Mahatthanatrakul, Tharinee Nontaput, Somchai Sriwiriyajan, Wibool Ridtitid, and Malinee Wongnawa

pp. 307 - 312

Abstract

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 at 0.17, 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 Avenoso
et al. (2000). Pharamcokinetic parameters i.e. C_max, AUC_0à48 and T_max
 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 guideline for bioequivalence study. The maximum concentration (C_max, 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 the plasma concentration-time curve (AUC_0→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 (T_max) of the innovator 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 C_max
 and AUC_0à48 of both preparations were 89.39-112.99% and 80.02-107.28% 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.