Aricept is indicated for the treatment of mild to moderate dementia of the Alzheimer s type. Donepezil enhances cholinergic function by inhibiting neuronal acetylcholinesterase and increasing acetylcholine concentrations in the brain. It is highly selective for central nervous system acetylcholinesterase, with less peripheral activity and a longer duration of inhibitory action than tacrine. The effects of donepezil may decrease as the disease progresses and fewer cholinergic neurons remain functional. Peak plasma concentrations are achieved within 3 to 5 hours.
Food appears to have no effect on the pharmacokinetics of donepezil.
Although elderly subjects have exhibited a larger volume of distribution and longer half-life, dosing adjustments do not appear to be necessary in these patients. Donepezil is extensively metabolized in the liver by oxidation via the cytochrome P450 2D6 and 3A4 isoenzymes and glucuronidation. Four major metabolites have been identified. Donepezil is excreted in the urine as unchanged drug and in the form of urinary metabolites. This phase was followed by a 6-week washout period.