A Randomized, Crossover, Single-Dose Bioequivalence Study of Two Extended-Release Tablets of Donepezil 23 mg in Healthy Human Volunteers under Fasting and Fed States

To assess the bioequivalence of two extended-release tablets of donepezil 23 mg, open label, randomized, single-dose, two-sequence, two-period cross-over studies under fasting (n=74) and fed (n=94) conditions in healthy adult human volunteers were conducted. Subjects were randomized to either of the two treatment arms (test or reference) separated by a washout period of 28 days. Blood samples were collected up to 72 h post-dose and plasma samples were analyzed for donepezil using a validated LC-MS/MS method. Pharmaco-kinetic parameters were derived using a non-compartmental approach. Bioequivalence was evaluated in 69 subjects in the fasting study, and 71 subjects in the fed study. In the fasting study, the 90% CI of Cmax and AUC0-72 were 82.50–90.10 and 92.38–98.60, respectively. Corresponding values in the fed study were 91.82–98.05 and 97.27–100.27. Based on the results, the test product (donepezil) met the US regulatory criteria of bioequivalence relative to the reference product (Aricept®) under both fasting and fed conditions.