Bioequivalence of two quinidine gluconate 324mg extended release formulations in healthy Brazilian volunteers under fed conditions: a pilot study

ABSTRACT

Background: Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with Class Ia activity. The present study was aimed at analyzing the bioequivalence of the proposed generic product Quinidine Gluconate 324mg Extended Release Tablets with the marketed product of Sun pharmaceuticals, USA.Methods: The design was an open, longitudinal, randomized, comparative study of two formulations in single dose of 324 mg, with a 5 days washout in between doses. The study was conducted in 12 healthy adult male and female Brazilian volunteers under fed conditions in Azidus Brasil, Valinhos, Brazil. Blood samples were collected post dose up to 36 hours for pharmacokinetic analysis and safety evaluation was done by assessing the adverse events and laboratory tests. A validated LC-MS/MS method was used to determine the plasma concentrations of Quinidine. Bioequivalence between the products was established by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-? values for the proposed generic product and marketed product.Results: The 90% confidence intervals found for the relation Test/Reference, were Cmax 80.78% to 109.07%, AUC0-t 86.04% to 104.24% and AUC0-? 86.25% to 104.71%. There were no clinically relevant changes in the vital parameters and the QT, QTc were not adversely affected and both the drug products were found to be safe and tolerable at the given strength.Conclusions: According to FDA´s guidelines for Bioequivalence research, the confidence intervals for Cmax, AUC0-t and AUC0-? ranged between 80.00-125.00%. The above limits obtained were within the accepted bio-equivalence limits.