Abstract
To assess the bioequivalence of two extended-release tablets of donepezil 23 mg, open label, randomized, single-dose, two-sequence, two-period crossover 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. Pharmacokinetic 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.
Highlights
Alzheimer’s Disease (AD) is a neurodegenerative disorder that primarily effects the elderly population [1]
Five subjects were withdrawn because of adverse events (AEs), one subject withdrew his consent prior to dosing in period II, and one subject who completed both the periods was not included in the statistical analysis due to non-compliance with the inclusion/exclusion criteria
Due to a higher rate of dropouts than expected, and given that period II of the study was yet to be completed, an additional group of 18 subjects was enrolled in order to obtain sufficient information to assess the bioequivalence of donepezil
Summary
Alzheimer’s Disease (AD) is a neurodegenerative disorder that primarily effects the elderly population [1]. With the immediate-release dosage forms, an initial spiking of donepezil in patients’ blood was observed, which may result in unwanted side effects (CNS and GIT problems) and reduced patient compliance [9]. To overcome these undesirable side effects associated with conventional immediate-release formulations and to provide a gradual release, an extended-release (ER) formulation of donepezil 23 mg was developed and approved for treating patients of moderate-to-severe AD [10]. The objective of the present study was to evaluate and compare the relative bioavailability of generic and branded formulations of donepezil 23 mg ER tablets in healthy, adult human volunteers (under fasting and fed states) for the purpose of marketing the generic formulation in the US
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