Sudo J, Iwase H, Terui J, Kakuno K, Soyama M, Takayama K, Nagai T
Department of Clinical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-02, Japan.
Eur J Pharm Sci. 1998 Dec;7(1):67-71. doi: 10.1016/s0928-0987(98)00007-4.
To improve compliance in administration of l-dopa, transdermal absorption of the agent was investigated in rats in vitro employing two-chamber diffusion cells in which the excised rat abdominal skin was mounted, and in vivo using an alcoholic hydrogel containing l-menthol. The in vitro study revealed that in presence of l-menthol (2%, W/W), ethanol (20 and 40%, V/V) accelerated transdermal penetration of l-dopa with an increase of its percentages. The in vivo study showed that when the l-dopa-hydrogel containing 2% l-menthol and 40% ethanol was attached on the skin, plasma levels of l-dopa and norepinephrine increased with the time elapsed; the level of dopamine increased and reached a plateau thereafter; and the level of epinephrine was unchanged. These in vitro and in vivo findings indicated that the hydrogel formulation of l-dopa provides new direction in treating Parkinson's disease.
为提高左旋多巴给药的依从性,在体外利用安装有切除大鼠腹部皮肤的双室扩散池对大鼠进行了该药物透皮吸收的研究,并在体内使用了含l-薄荷醇的酒精水凝胶进行研究。体外研究表明,在l-薄荷醇(2%,W/W)存在的情况下,乙醇(20%和40%,V/V)随着其百分比的增加加速了左旋多巴的透皮渗透。体内研究表明,当含有2% l-薄荷醇和40%乙醇的左旋多巴水凝胶贴于皮肤上时,左旋多巴和去甲肾上腺素的血浆水平随时间推移而增加;多巴胺水平升高并随后达到平台期;肾上腺素水平未发生变化。这些体外和体内研究结果表明,左旋多巴水凝胶制剂为帕金森病的治疗提供了新的方向。