Abstract

Objective: The objective of the study was to evaluate bioequivalence of two strengths (1 and 2 mg) of oral risperidone tablet formulations (test product manufactured by Vita-Invest, S.A., Barcelona, Spain, reference product manufactured by Janssen-Cilag Ltd., UK). Subjects and methods: In each of the 2 studies, 30 healthy volunteers were administered 1 or 2 mg, respectively, of test or reference formulation under fasting conditions in an open, two-way crossover, controlled, randomized and single-site fashion. Blood withdrawal was performed prior to dosing as well as 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 5 h, 8 h, 12 h, 16 h, 24 h, 48 h, 72 h, and 96 h after drug administration. Plasma concentrations of risperidone and its metabolite 9-hydroxy-risperidone were analyzed using LC/MS/MS. Descriptive data of AUC_0-t, AUC_0-¥, C_max, and C_max/AUC_0-¥ were log-transformed to evaluate bioequivalence based on the ratios of the geometric means of test and reference formulations. t_max was analyzed using nonparametric methods. Results: The results show that in both studies, 1 and 2 mg formulations, the 90% confidence intervals for the geometric means ratios of the test and reference products for both the parent compound risperidone and its metabolite 9-hydroxy-risperidone were all within the bioequivalence acceptance criteria of 0.80 – 1.25 of the European CPMP and the US FDA guidelines, with the exception of t_max for risperidone parent compound in the 2 mg formulation, which was slightly suprabioequivalent for test formulation. Conclusion: This study demonstrated the bioequivalence between the test and the reference product of risperidone of both 1 and 2 mg formulations. Both formulations of each strength may, therefore, be prescribed interchangeably.

Author Details

Authors

• M. Cánovas¹
• J. Delgadillo²
• F. Torres³
• N. Riba⁴
• J. Cebrecos⁵
• P. Pelagio⁶
• F. Cabré¹

Departments

• ¹ R&D area, Laboratorios Lesvi, S.L., Invent Farma Group,
• ² Vita-Invest, S.A.,
• ³ Laboratori de Bioestadistica i Epidemiologia, Universitat Autónoma de Barcelona, Servei de Farmacologia Clínica, IDIBAPS, Hospital Clinic, Barcelona,
• ⁴ Servei de Farmacologia Clínica UASP, Hospital Clinic, Barcelona,
• ⁵ Phase I Unit of Laboratorio Dr. F. Echevarne Análisis, S.A.,
• ⁶ Bioanalysis-Pharmacokinetic Unit of Laboratorio Dr. F. Echevarne Análisis S.A., Barcelona, Spain

Address

M. Cánovas, PhD; Biological Development Manager of Laboratorios Lesvi, S.L., Avda.,
Barcelona 69, 08970 Sant Joan Despí, Barcelona, Spain
Email: [email protected]

Citation