title: Donepezil dosing strategies: pharmacokinetic considerations.
abstract: Donepezil (Aricept) is a cholinesterase inhibitor approved for the treatment of Alzheimer's disease. Immediate release formulations of 5- and 10-mg tablets were approved by the Food and Drug Administration in the United States in 1996. In July 2010, the Food and Drug Administration approved a 23-mg sustained release (SR) formulation. The SR formulation may provide additional benefit to patients receiving 10 mg daily but the incidence of adverse reactions is increased. We derived plasma concentration profiles for higher dose immediate-release formulations (15 mg once daily, 10 mg twice daily, and 20 mg once daily) and for the profile anticipated to result from the 23-mg SR formulation. Our model predicts similar steady-state concentration profiles for 10 mg twice daily, 20 mg once daily, and 23 mg SR once daily. This provides the theoretical basis for incremental immediate release dose escalation to minimize the emergence of adverse reactions and the potential to offer a cost-effective alternative to the SR formulation with currently approved generic immediate release formulations.
authors.affiliation: Division of Geriatric Medicine and Clinical Pharmacology, Winthrop University Hospital, Mineola, NY; Department of Medicine, Stony Brook University, Stony Brook, NY. Electronic address: igomolin@winthrop.org.
authors.forename: Irving H
authors.initials: IH
authors.lastname: Gomolin
authors.affiliation: Department of Clinical Pharmacy Practice, St. John's University College of Pharmacy & Allied Health Professions, Queens, NY.
authors.forename: Candace
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, NY; Applied Bench Core, Winthrop University Hospital, Mineola, NY.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jeitner
mesh_terms: D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000191:economics / Q000493:pharmacokinetics*; D003362:Cost-Benefit Analysis; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000097:blood / Q000191:economics / Q000493:pharmacokinetics*; D008962:Models, Theoretical; D010880:Piperidines / Q000008:administration & dosage* / Q000097:blood / Q000191:economics / Q000493:pharmacokinetics*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil