Pharmacokinetic and pharmacodynamic evaluation of donepezil for the treatment of Alzheimer's disease.

INTRODUCTION: Donepezil is a highly selective acetylcholinesterase inhibitor and one of the only four drugs currently approved for treatment of Alzheimer's dementia. Providing high bioavailability and a very long half-time, donepezil is regarded as effective and well tolerable in Alzheimer's disease patients, even in difficult clinical conditions such as hepatic or renal impairment. It moderately improves cognitive and global functioning scores in patients with mild to moderate Alzheimer's disease over the course of 6 - 12 months, with open-label extension studies suggesting effects of even longer duration. AREAS COVERED: We summarized relevant pharmacokinetic, pharmacodynamic, clinical trial and neuroimaging data of donepezil. A literature search was performed in the PubMed database; articles published until October 2013 have been considered for this review. Moreover, references from original work and reviews have been searched for further relevant literature. EXPERT OPINION: Donepezil is one of the most frequently prescribed anti-dementia drugs. The recent additional approval of the 23 mg formulation will expand its use in patients with moderate to severe Alzheimer's disease. After numerous Phase III study failures of novel disease-modifying drugs for Alzheimer's disease, donepezil is likely going to stay a first-line therapeutic option in Alzheimer's disease in the upcoming years.