Transdermal Delivery Laboratory, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA 30341-4155, USA.
Int J Pharm. 2013 Sep 10;453(2):395-9. doi: 10.1016/j.ijpharm.2013.05.029. Epub 2013 Jun 2.
The nature of Alzheimer's disease limits the effectiveness of available oral treatments. The aim of this study was to assess the feasibility of transdermal iontophoretic delivery of donepezil in a hairless rat model as a potential treatment modality in Alzheimer's and to evaluate the effect of current densities on its pharmacokinetics. Donepezil loaded integrated Wearable Electronic Drug Delivery (WEDD(®)) patches supplied current levels of 0, 0.13, 0.26 and 0.39 mA. Plasma extracted donepezil was analyzed by HPLC. Noncompartmental analysis was used to characterize disposition of the drug. The amount delivered across hairless rat skin and areas under the curve (AUC) were found to rise in proportion to the current levels. Peak plasma levels of 0.094, 0.237 and 0.336 μg/ml were achieved at 0.13, 0.26 and 0.39 mA respectively. Time to peak plasma concentrations was after termination of current and same for all current levels. Transdermal elimination half-life was significantly increased from the true value of 3.2h due to depot formation, prolonging complete absorption of the drug. Donepezil was successfully delivered iontophoretically at levels sufficient to produce pharmacodymanic effect. Pharmacokinetic analysis demonstrated linear kinetics at the current levels used and flip flop kinetics following iontophoretic administration.
阿尔茨海默病的性质限制了现有口服治疗方法的有效性。本研究旨在评估将多奈哌齐经皮离子电渗递送至无毛大鼠模型作为阿尔茨海默病潜在治疗方法的可行性，并评估电流密度对其药代动力学的影响。多奈哌齐负载的集成式可穿戴电子药物输送（WEDD(®)）贴片提供 0、0.13、0.26 和 0.39 mA 的电流水平。通过 HPLC 分析提取的多奈哌齐等离子体。非房室分析用于描述药物的处置。发现经无毛大鼠皮肤输送的药物量和曲线下面积（AUC）与电流水平成正比增加。在 0.13、0.26 和 0.39 mA 时，分别达到 0.094、0.237 和 0.336μg/ml 的峰值血浆水平。达到峰值血浆浓度的时间是在电流终止后，所有电流水平相同。由于储库形成，经皮消除半衰期显著延长至 3.2h 的真实值，从而延长了药物的完全吸收。多奈哌齐经离子电渗成功递送至足以产生药效的水平。药代动力学分析表明，在使用的电流水平下呈现线性动力学，在离子电渗给药后呈现翻转动力学。
