Bioequivalence evaluation of 2 tablet formulations of entecavir in healthy chinese volunteers: a single-dose, randomized-sequence, open-label crossover study.

Abstract

A randomized, 2-way crossover study was conducted in healthy Chinese male volunteers to evaluate the bioequivalence of a new generic formulation of entecavir (CAS 142217-69-4) tablets (test) and the available branded formulation (reference) to meet the requirements for marketing the test product in China. Test and reference tablets were administered as a single dose on 2 treatment days separated by a 2-week washout period. Blood samples were collected for a period of 24 h following drug administration. Plasma concentration of entecavir was determined by a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method. Pharmacokinetic parameters were calculated using a noncompartmental model. Bioequivalence was determined by calculating 90% CIs for the ratios of Cmax, AUC0-t and AUC0-∞ values for the test and reference products. Tolerability was assessed by monitoring vital signs, laboratory tests and interviews with the volunteers before administration and every 2 h during the study. The 90% CIs of entecavir for Cmax, AUC0-t and AUC0-∞ were 95.2-106.9%, 98.4-104.6% and 97.3-104.4%, respectively, which fell within the interval of 80-125%. No clinically important adverse effects were reported. These results suggested that the test formulation of entecavir tablets met the regulatory criterion for bioequivalence to the reference formulation.