Bioequivalency Study for Inhaled Drugs: A Pharmacodynamic Approach

Abstract

The study was performed to evaluate the bioequivalence of two marketed dry powder inhaler products formoterol 6 mcg associated with and budesonide 200 mcg Alenia ® from Biosintetica Farmaceutica Ltd. and Symbicort ®. AstraZeneca, Brazil) in 27 volunteers patients of both sexes. The study used an open, randomized, 2 period crossover balanced design, with a 36 days wash out period between the doses. The pharmacodynamic evaluation of formoterol and budesonide was performed by Spirometry, comparing the response of the two products to prevent wheezing illness (bronchial obstruction) induced by methacholine. The mean ratio of AUC 0-t parameters and 90% confidence intervals were calculated to determine the pharmacodynamic responses. Geometric mean for the test and reference formulation of formoterol with budesionide in the form of dry powder in capsule was AUC0-t ratio (test/ reference: 101.70% [98.53% - 104.98%]). We concluded that the formulations Alenia® and Symbicort® are therapeutically equivalent, considering the confidence intervals (90%) of the ratios between the geometric means of the test and reference formulations, the AUC 0-t parameter, and taking into account this is a pharmacodynamic study, in which intervals to determine therapeutic equivalence have not been established yet. The limits of the confidence interval of the parameters studied are within the range established by RE 1170 (April 2006/ANVISA) for pharmacokinetic parameters.