Abstract: Aim To study percutaneous absorption and metabolism of ketoprofen isopropyl ester (KPE) via excised nude mouse’s and monkey’s skin. Methods Excised skin was prepared by surgical excision and enzyme digestion. Side-by-side diffusion cells were used for in vitro permeation studies. The concentrations of KPE and its metabolite in samples were assayed by HPLC. Results All KPE penetration through whole thickness skin and stripped skin was metabolized to ketoprofen (KP), the concentration of which in the receiver solution increased linearly with time. As to the nude mouse skin, the steady state flux of KP through whole thickness skin was 2-5 times that of KPE through the whole thickness skin, but the KP and KPE remaining in the whole thickness skin after the finishing of KPE penetration was 22-2 times in compared with the KP remaining in the whole thickness skin after the finishing of KP penetration. The rate of formation of the steady state KP from KPE through dermis was significantly lower than that of KPE through the whole thickness skin. In the monkey skin, the rate of formation of the steady-state KP from KPE through the whole thickness skin was 0-7 times that from KPE through stripped skin. The KP and KPE remaining in the whole thickness skin after the finishing of KPE penetration was 2-0 times that in the stripped skin after the finishing of KPE penetration. The rate of formation of the steady state KP from KPE through dermis was lower than that from KPE through the whole thickness skin and the stripped skin, the KP remaining in dermis after the finishing of KPE penetration was also significantly lower than the KP remaining in the whole thickness skin and the stripped skin after the finishing of KPE penetration. Conclusion KP esters are of benefit to improve the local action of KP, and skin esterase metabolism mainly develops in the epidermis.

Key words: ketoprofen, ketoprofen, ketoprofen isopropyl ester, ketoprofen isopropyl ester, skin permeation, skin permeation, skin metabolism, skin metabolism