Kim Yo Han, Choi Hee Youn, Lim Hyeong-Seok, Lee Shi Hyang, Jeon Hae Sun, Hong Donghyun, Kim Seong Su, Choi Young Kweon, Bae Kyun-Seop
Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
iCure Pharmaceutical lncorporated, Anseong, Gyeonggi-do, Republic of Korea.
Drug Des Devel Ther. 2015 Mar 10;9:1419-26. doi: 10.2147/DDDT.S78555. eCollection 2015.
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.
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.
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.
The donepezil patch appeared to be generally well tolerated and adhesive. Pharmacokinetic analysis of the donepezil patch demonstrated linear kinetics.
多奈哌齐是一种用于治疗阿尔茨海默病的乙酰胆碱酯酶抑制剂。这项随机、单盲、安慰剂对照、单剂量、剂量递增研究的目的是调查多奈哌齐贴片在健康男性受试者中的安全性、耐受性和药代动力学。
每位健康男性受试者接受一片43.75 mg/12.5 cm²、87.5 mg/25 cm²或175 mg/50 cm²的多奈哌齐透皮贴片（贴片持续72小时）。在贴片应用后长达312小时内采集系列血样。采用经过验证的液相色谱 - 串联质谱法测定血浆中多奈哌齐的浓度。通过非房室分析获得药代动力学参数。在整个研究过程中评估贴片的耐受性以及贴片的性能（粘附性、皮肤刺激性、贴片中多奈哌齐的残留量）。
36名健康受试者完成了该研究。贴片应用后，血浆多奈哌齐的最大浓度（Cmax）和曲线下面积（AUC）呈剂量比例增加。达到Cmax的中位时间约为74 - 76小时（贴片移除后约2 - 4小时），平均t1/2β约为63.77 - 93.07小时。72小时后贴片中多奈哌齐的平均残留量约为负荷剂量的73.9% - 86.7%。既没有严重不良事件，也没有导致停药的不良事件。97.2%的受试者贴片的皮肤粘附性良好。贴片移除后的所有皮肤刺激均为轻度，且在研究期间得到缓解。
多奈哌齐贴片似乎总体耐受性良好且具有粘附性。多奈哌齐贴片的药代动力学分析显示为线性动力学。
