A novel administration route for edaravone: I. Effects of metabolic inhibitors on skin permeability of edaravone

We examined the effects of metabolic inhibitors on skin permeation of edaravone. SKF-525A, diclofenac sodium (DIC) and indomethacin (IND) were added to supernatant fluid (SF) of hairless rat (HR) skin homogenate. l-Cysteine (l-Cys) and benzotriazole (BTA), as pharmaceutical additives, were added to HR skin homogenate SF, and incubated at 37 °C for 30 min. Km and Vmax values were calculated. For determination of edaravone skin permeation from edaravone/hydroxypropyl-β-cyclodextrin (HPβCD) complex solution, HR skin was placed in a Franz diffusion cell, and kept at 37 °C. Edaravone/HPβCD solution that contained l-Cys was put into the donor side. The relative activity in skin homogenate SF after co-treatment with IND and SKF-525A decreased to 40.8% of the control. However, DIC and IND had a weak inhibitory effect. For inhibition of edaravone metabolism, l-Cys and BTA had no effect on Km value, but Vmax was significantly decreased compared with controls (*P < 0.05, Tukey–Kramer test). The edaravone skin permeation rate and permeability coefficient from edaravone/HPβCD complex solution with inhibitor were significantly increased compared with those without inhibitor. We suggest that the metabolism inhibitor was useful for the transdermal delivery of edaravone.