Bioequivalence evaluation of two strengths of risperidone tablet formulations in healthy volunteers.
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).


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 AUC0-t, AUC0- yen, Cmax, and Cmax/AUC0- yen were log-transformed to evaluate bioequivalence based on the ratios of the geometric means of test and reference formulations. tmax 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 tmax for risperidone parent compound in the 2 mg formulation, which was slightly suprabioequivalent for test formulation.


CONCLUSIONS
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.
Cánovas
M
M
R&D area, Laboratorios Lesvi, S.L., Invent Farma Group, Universitat Autónoma de Barcelona, Servei de Farmacologia Clínica, IDIBAPS, Hospital Clinic, Barcelona, Spain. mcanovas@lesvi.com
Delgadillo
J
J
Torres
F
F
Riba
N
N
Cebrecos
J
J
Pelagio
P
P
Cabré
F
F
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D005062:European Union; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D007555:Isoxazoles / Q000493:pharmacokinetics*; D008297:Male; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000493:pharmacokinetics*; D018967:Risperidone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D013607:Tablets; D018967:Risperidone; D000068882:Paliperidone Palmitate