title: Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers.
abstract: BACKGROUND
  Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer's disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects.
  
  
  METHODS
  Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods) of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), or 175 mg/50 cm(2). Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch) were assessed throughout the study.
  
  
  RESULTS
  The study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax) and the area under the curve (AUC) increased in a dose-proportional manner. Median time to Cmax was ~74-76 hours (~2-4 hours after patch removal), and mean t1/2β was ~63.77-93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%-86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period.
  
  
  CONCLUSIONS
  The donepezil patch appeared to be generally well tolerated and adhesive. Pharmacokinetic analysis of the donepezil patch demonstrated linear kinetics.
authors: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors: Yo Han
authors: YH
authors: Kim
authors: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors: Hee Youn
authors: HY
authors: Choi
authors: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors: Hyeong-Seok
authors: HS
authors: Lim
authors: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors: Shi Hyang
authors: SH
authors: Lee
authors: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors: Hae Sun
authors: HS
authors: Jeon
authors: iCure Pharmaceutical lncorporated, Anseong, Gyeonggi-do, Republic of Korea.
authors: Donghyun
authors: D
authors: Hong
authors: iCure Pharmaceutical lncorporated, Anseong, Gyeonggi-do, Republic of Korea.
authors: Seong Su
authors: SS
authors: Kim
authors: iCure Pharmaceutical lncorporated, Anseong, Gyeonggi-do, Republic of Korea.
authors: Young Kweon
authors: YK
authors: Choi
authors: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors: Kyun-Seop
authors: KS
authors: Bae
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D002853:Chromatography, Liquid; D000077265:Donepezil; D004361:Drug Tolerance; D064368:Healthy Volunteers; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D053719:Tandem Mass Spectrometry; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: donepezil; healthy subjects; pharmacokinetics; transdermal patch