title: A novel administration route for edaravone: I. Effects of metabolic inhibitors on skin permeability of edaravone.
abstract: 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 degrees C for 30 min. K(m) and V(max) values were calculated. For determination of edaravone skin permeation from edaravone/hydroxypropyl-beta-cyclodextrin (HPbetaCD) complex solution, HR skin was placed in a Franz diffusion cell, and kept at 37 degrees C. Edaravone/HPbetaCD 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 K(m) value, but V(max) was significantly decreased compared with controls (*P<0.05, Tukey-Kramer test). The edaravone skin permeation rate and permeability coefficient from edaravone/HPbetaCD 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.
authors.affiliation: Reserch & Development Division, Mikasa Seiyaku Co., Ltd., 2-3-1 Toyotama-Kita, Nerima-ku, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sato
authors.forename: Keizo
authors.initials: K
authors.lastname: Mizuno
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Ishii
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077553:Edaravone; D008297:Male; D010539:Permeability / Q000187:drug effects; D011335:Proadifen / Q000008:administration & dosage; D051381:Rats; D054772:Rats, Hairless; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*
chemical_list: D011335:Proadifen; D000077553:Edaravone; D000983:Antipyrine