Pharmacokinetics

Absorption Distribution Metabolism Excretion Special Population Other Details (N/A)

Absorption

Maximum plasma levels are reached approximately 3 to 4 hours after oral administration. Plasma concentrations and area under the curve rise in proportion to the dose. The terminal disposition half-life is approximately 70 hours, thus, administration of multiple single-daily doses results in gradual approach to steady-state. Approximate steady-state is achieved within 3 weeks after initiation of therapy. Once at steady-state, plasma donepezil hydrochloride concentrations and the related pharmacodynamic activity show little variability over the course of the day. Food does not affect the absorption of donepezil hydrochloride.


Distribution

Donepezil hydrochloride is approximately 95% bound to human plasma proteins. The plasma protein binding of the active metabolite 6-O-desmethyldonepezil is not known. The distribution of donepezil hydrochloride in various body tissues has not been definitively studied. However, in a mass balance study conducted in healthy male volunteers, 240 hours after the administration of a single 5 mg dose of 14C-labeled donepezil hydrochloride, approximately 28% of the label remained unrecovered. This suggests that donepezil hydrochloride and/or its metabolites may persist in the body for more than 10 days.


Metabolism

Donepezil is hepatically metabolized. The major metabolites of donepezil include M1 and M2 (via O-dealkylation and hydroxylation), M11 and M12 (via glucuronidation of M1 and M2 respectively), M4 (via hydrolysis) and M6 (via N-oxidation). Plasma donepezil concentrations decline with a half-life of approximately 70 hours.

Sex, race and smoking history have no clinically significant influence on plasma concentrations of donepezil hydrochloride.


Excretion

The predominant route for the elimination of both parent drug and its metabolites is renal, as 79% of the recovered dose was found in the urine with the remaining 21% found in the feces. Moreover, the parent compound, donepezil, is the predominant elimination product in urine. There was a relationship noted between body weight and clearance. Over the range of body weight from 50 kg to 110 kg, clearance increased from 7.77 L/h to 14.04 L/h, with a value of 10 L/hr for 70 kg individuals.


Special Population

The pharmacokinetics of donepezil has not been formally studied in healthy elderly subjects, or in Alzheimer’s or vascular dementia patients. However mean plasma levels in patients closely agreed with those young healthy volunteers.

Disclaimer

This website is intended for healthcare professionals only. To proceed, please indicate your PRC (Professional Regulation Commission) number for verification purposes.

By clicking "Continue," you consent to the collection and use of your PRC number and any other personal data provided for the purpose of confirming your professional credentials and accessing restricted content in this site. Your data will be handled in accordance with our Data Privacy Policy and applicable data protection laws.

If you do not consent to these terms, please exit the site.

Oops! We could not locate your form.