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®, a test tablet formulation of donepezil hydrochloride 10 mg, with those of Aricept®, the reference tablet formulation of donepezil hydrochloride 10 mg, in healthy Korean male volunteers. A randomized, singledose, 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 μg/L (mean±SD), respectively, while AUC 288h was 1080.14±229.77 and 1043.07±242.28 μg·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.

Model-Based Equivalent Dose Optimization to Develop New Donepezil Patch Formulation

“…A recent study using a population PK model of oral donepezil administration estimated an oral clearance of 12 L/h [16]. Another report stated that donepezil hydrochloride clearance was 9.65 L/h after administration of a 10 mg tablet [17]. The NCA PK parameters were 10 L/h (CLss) and 560 L (Vss) after oral administration of 10 mg drug.…”

Study on the preparation and drug release property of Modified PEG-DA based hydrogels

“…Donepezil has been investigated to be sufficient for enhancing of cognitive impairment and memory loss in patients with Alzheimer's disease. It is well efficient when 5 mg of the drug is used once daily (22)(23)(24)(25)(26)(27). 1.…”