薬理と治療

Abstract

Background　Donepezil is a cholinesterase inhibitor indicated for Alzheimer-type dementia. No transdermal patches of donepezil have been approved in Japan. Objectives　To evaluate the safety and linear pharmacokinetics of repeated applications of donepezil patch at 3 dosages in 3 sizes in healthy, elderly, Japanese men. Methods　A phase 1, open-label, single-center, 3-period crossover, multiple-dose study was conducted in Japan between March 2018 and August 2018. Eligible healthy subjects aged≥65 years were randomly assigned to one of 3 treatment sequences and received repeated application of donepezil patch at 13.75 mg╱22 cm2, 27.5 mg╱44 cm2, or 55.0 mg╱88 cm2 once daily for 17 days in each period with a washout period of≥19 days. Donepezil patches were applied to a total of 8 sites in the back with an interval of 7 days between applications to the same site. Results　Of 36 randomized subjects, 32 completed the study. Analyses using the power model showed the dose proportionality of plasma donepezil Cmax and AUC0-24h. Drug-related adverse events（AEs）included erythema, nausea, and vomiting（3 subjects each）, pruritus（2 subjects）, and decreased appetite and dizziness（1 subject each）. All drug-related AEs were Grade 1 or 2 in severity. Skin manifestations on the patch surface containing donepezil were overall mild, and resolved within 3 days in the majority of the subjects. Conclusions　Linear pharmacokinetics of donepezil patch was established for Cmax and AUC0-24h. No new safety concerns were identified for donepezil patch.（Jpn Pharmacol Ther 2022；50：1801‒15）