Análise estatística de um estudo de bioequivalência farmacêutica da quetiapina em delineamento crossover 2x2

Abstract

The registration of generic and similar medicines requires the submission of documentation and criteria to be met, required by the National Health Surveillance Agency (ANVISA), to ensure quality, safety and efficacy. The pharmaceutical bioequivalence study, carried out for comparison between the test formulations (generic or similar) and the reference formulations, consists of demonstrating the equivalence of bioavailability between the two formulations, under the same experimental design, so they can be interchangeable. Some premises, duly established by ANVISA resolutions, must be followed for the quality and reliability of the results of the study. The statistical analysis of this study evaluates the (residual) sequence, period and formulation effects of the pharmacokinetic parameters Cmax, ASC0-t and ASC0-inf using the variance analysis (ANOVA). It is concluded that there is bioequivalence between two formulations when the 90% confidence interval for the geometric means ratio of each of the pharmacokinetic parameters is included in the range of values from 0.8 to 1.25 (80 to 125%). As an application, we present the bioequivalence study of Quetiapine hemifumarate (25 mg coated tablet, single dose), in 2x2 crossover design, with 48 healthy volunteers of both sexes. No sequence, period or formulation effect was observed, and 90% confidence intervals for the three pharmacokinetic parameters were found to result within the bioequivalence ranges. We conclude that the test and reference formulations are bioequivalent and are also interchangeable.