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 pharmacokinetics of repeated applications of donepezil patch compared with donepezil hydrochloride oral tablet in healthy, elderly, Japanese men. Methods　A phase 1, open-label, single-center, multiple-dose study was conducted in Japan between March 2017 and August 2017. In period 1, eligible healthy subjects aged ≥65 years received repeated applications of donepezil patch 27.5 mg once daily for 17 days at a total of 8 sites in the back with an interval of 7 days between applications to the same site. After a washout period of ≥19 days, each subject proceeded to period 2 and received multiple doses of donepezil hydrochloride oral tablet 3 mg once daily for 7 days, followed by 5 mg once daily for 14 days. Results　A total of 12 and 11 subjects completed periods 1 and 2, respectively. The geometric mean ratio of plasma donepezil AUC0-24h on the last dosing day of period 1 to period 2 was 0.956（90％ confidence interval: 0.819, 1.116）. Drug-related adverse events（AEs）in period 1 included erythema（58.3％）and abdominal discomfort, nausea, vomiting, edema, and hepatic function abnormal（8.3％ each）. All drug-related AEs were Grade 1 and recovered without treatment. No AEs were reported in period 2. Conclusions　The pharmacokinetics of donepezil patch was similar to that of donepezil hydrochloride oral tablet as assessed by AUC0-24h. No new safety concerns were identified for donepezil patch.（Jpn Pharmacol Ther 2022；50：1787‒99）