Comparative Bioavailability Study of Two Tablet Formulations of Digoxin

Abstract

This investigation was carried out to evaluate the bioavailability of the generic product of digoxin 0.25 mg (cardixin) relative to a reference product, lanoxin (0.25 mg) tablets. The two formulations were found to be similar in in vitro assay (dissolution) as stipulated by USP XXIII. The comparison is carried out on 12 healthy male volunteers, who received a single dose (0.25 mg) of cardixin (product A) lanoxin (product B) as a reference product orally in the fasting state, in a randomized balanced two-way crossover design. After dosing, serial blood samples were collected for a period of 12 hr. Plasma samples were analyzed for digoxin by a sensitive and validated enzyme immunoassay method (ELISA). The maximum plasma concentration curve, up to the last measurable concentration (AUC(0-24)), was analyzed under the assumption of a multiplicative model. The time to maximum concentration (Tmax) was analyzed, assuming an additive model. The parametric confidence intervals (90%) of the mean values of the pharmacokinetic characteristics (AUC(0-12) and Cmax) for A:B ratio were, in each case, well within the bioequivalence acceptable range of 80-125%.