Bioequivalence study of Donepezil hydrochloride in healthy Korean volunteers

ABSTRACT

Donepezil is a centrally acting, reversible acetylcholinesterase inhibitor that is widely used for treating Alzheimer's disease. This study aimed to compare the pharmacokinetics of Bastia(R), a test tablet formulation of donepezil hydrochloride 10 mg, with those of Aricept(R), the reference tablet formulation of donepezil hydrochloride 10 mg, in healthy Korean male volunteers. A randomized, single-dose, two-way crossover study was conducted in 32 subjects. Subjects received a single dose of either test or reference compound and the alternate drug after a 4-week washout period. Serial blood samples for pharmacokinetic analysis were collected prior to dosing and periodically for 288 h after dosing for measurement of the plasma concentrations of donepezil. A non-compartmental method was used to estimate the pharmacokinetic parameters. The maximum concentration (C(max)) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(288h)) for the two formulations were compared to evaluate bioequivalence. The C(max) of the test and reference drugs were 27.58+/-7.46 and 26.35+/-6.51 microg/L (mean+/-SD), respectively, while AUC(288h) was 1080.14+/-229.77 and 1043.07+/-242.28 microg.h/L (mean+/-SD), respectively. The geometric mean ratios (90% confidence interval) of the C(max) and AUC(288h) of the two tablets were 1.043 (0.990-1.099) and 1.039 (1.013-1.065). In conclusion, the newly formulated tablet of donepezil hydrochloride 10 mg is bioequivalent to the currently marketed 10 mg tablet.