Bioequivalence Between Two Prolonged Release Tablets of Darifenacin in Healthy Subjects Under Fasting and Fed Conditions

Abstract

Bioavailability in different formulations of darifenacin 15 mg prolonged release tablets was compared in two bioequivalence studies, one under fasting conditions and the other after a standard breakfast. Both studies were single dose, randomized, open label, two-period crossover, with Brazilian males and females healthy subjects. Blood samples were taken during 72 h and plasmatic concentrations were determined using a validated UPLC-MS/MS method. Confidence intervals (CI90%) for the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC0-t) were determined by calculating log-transformed data. In the fast study, the ratios and 90% CI for the geometric mean was 94.82% (86.08-104.46%) for Cmax and 92.49% (84.68-101.03%) for AUC0-t. In the fed study, the ratios and 90% CI for the geometric mean was 94.41% (85.96-103.70%) for Cmax and 94.37% (88.79-100.31%) for AUC0-t. Under fast and fed conditions, the test (darifenacin 15 mg prolonged release tablets, Zodiac Produtos FarmacAauticos S.A.) and reference (Enablex® 15 mg prolonged release tablets, Novartis BiociAancias S.A.) formulations were considered bioequivalent since the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125% according to FDA and to ANVISA.