Our aim was to assess the feasibility of transdermal delivery of donepezil and evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of donepezil patch in vitro and in vivo. Donepezil patches were applied to the skin of rabbits and humans for 7 days, then, the PK profiles were observed in a dose-dependent manner. Donepezil was continuously released from the patch for 7 days as compared to oral administration in hairless rats and rabbits. In hairless rats, peak acetylcholinesterase (AChE) inhibition of 34.7±2.0% was observed within 8 h after oral administration of 4 mg/head donepezil, and lasted for less than 24 h, consistent with changes in the plasma donepezil concentration. Peak AChE inhibition by the donepezil patch was equivalent to that in the orally administered group. Donepezil was released continuously from the patch for 7 days with a linear PK in both rats and rabbits. AChE activity inhibition was dependent on donepezil plasma concentration. The data exhibited excellent PK/PD correlation. There was no dermal irritation (erythema/edema) in placebo or donepezil patch group during the study period in minipigs. Thus, Dong-A's donepezil patch appeared to be generally safe and was well tolerated.