石杉碱甲在不同种属皮肤的体外渗透动力学

 目的比较石杉碱甲(Hup-A)在小鼠、犬与人离体皮肤的渗透动力学,为Hup-A透皮吸收贴片的处方设计及其药效学、药动学的研究提供依据。方法采用Valia-Chien双室渗透池进行离体皮肤渗透试验,HPLC法检测渗透液中Hup-A的浓度,比较Hup-A在不同种属皮肤的渗透动力学。结果Hup-A在小鼠皮肤渗透速度最快,渗透速率最大,在3h就达峰值。在犬与人离体皮肤,Hup-A的渗透动力学曲线相近,渗透速率无统计学差异(P>0.05)。Hup-A在12～24h达最大速率后,于84h内维持一个较为平稳的渗透速率。结论以小鼠为对象的药效学试验应根据小鼠皮肤的渗透动力学参数设计实验方案,犬用于Hup-A透皮吸收制剂药动学研究是较为理想的选择,犬皮肤还可代替人皮肤作为Hup-A透皮贴片前期处方筛选。

Skin Permeation of Huperzine A in Different Skin Species

OBJECTIVE To study the skin permeation of Huperzine A (Hup-A) in vitro transdermal patches in mouse,dog and human skins,and provide data for the formulation screening,pharmacodynamic and pharmacokinetics studies.METHODS In vitro permeation studies were conducted using two-chambered Valia-Chien glass diffusion cell assembly in three different skin species. Hup-A concentrations were determined by HPLC method,and permeation rates of Hup-A were calculated and compared.RESULTS The penetration of Hup-A through mouse skin was quicker and permeation rate was higher than that through dog and human skins. The permeation rate-time profiles of Hup-A through dog and human skins were similar.Hup-A permeation rate reached the maximum approximately 12~24 h following the application of the patch,and then maintained for up to 84 h.CONCLUSION The Hup-A permeation rates of mouse and human skins were greatly different. So,the mouse-based pharmacodynamics should be designed according to the in vitro Hup-A skin permeation study. In addition,the similarity of Hup-A skin permeation between dog and human skin supports the use of the dog as a species for evaluating the pharmacokinetics of transdermally-administered Hup-A.