Winblad Bengt, Machado João Carlos
Karolinska Institutet Alzheimer's Disease Research Center (KI-ADRC), Floor 5, S-14157, NOVUM, Huddinge, Sweden.
Expert Opin Drug Deliv. 2008 Dec;5(12):1377-86. doi: 10.1517/17425240802542690.
Cholinesterase inhibitors such as rivastigmine and donepezil exhibit a dose-response relationship, with higher doses of the drugs demonstrating greater efficacy. Transdermal patches provide smooth continuous drug delivery, with the potential to offer efficacious levels of drug exposure while avoiding the peaks and troughs associated with side effects. As a small, lipophilic and hydrophilic molecule, rivastigmine (C14H22N2O2) is chemically well-suited to transdermal delivery. The technology underlying the rivastigmine patch allows it to be discreetly small and thin. The target dose 9.5 mg/24 h rivastigmine patch has a diameter of just 3.5 cm and a surface area of 10 cm2. A large randomized controlled trial has demonstrated that the target dose 9.5 mg/24 h rivastigmine patch provided similar efficacy to the highest rivastigmine capsule doses, yet with three times fewer reports of nausea and vomiting. Thus, the rivastigmine patch enables quick and easy access to high dose efficacy. The skin tolerability profile is good, and the patch has demonstrated excellent adhesion. The apparent success of rivastigmine patch, in terms of clinical utility and patient acceptability, suggests that it may mark the next generation of dementia treatment.
卡巴拉汀和多奈哌齐等胆碱酯酶抑制剂呈现剂量反应关系，药物剂量越高疗效越显著。透皮贴剂可实现药物的平稳持续递送，有可能提供有效的药物暴露水平，同时避免与副作用相关的血药浓度峰谷波动。卡巴拉汀（C14H22N2O2）作为一种兼具亲脂性和亲水性的小分子，在化学性质上非常适合透皮给药。卡巴拉汀贴剂所基于的技术使其尺寸小巧且轻薄。目标剂量为9.5毫克/24小时的卡巴拉汀贴剂直径仅为3.5厘米，表面积为10平方厘米。一项大型随机对照试验表明，目标剂量为9.5毫克/24小时的卡巴拉汀贴剂与最高剂量的卡巴拉汀胶囊疗效相当，但恶心和呕吐的报告数量减少了三分之二。因此，卡巴拉汀贴剂能够快速便捷地实现高剂量疗效。其皮肤耐受性良好，贴剂表现出优异的黏附性。卡巴拉汀贴剂在临床实用性和患者可接受性方面的明显成功表明，它可能标志着痴呆症治疗的新一代产品。
