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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.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Sato T,Mizuno K,Ishii F

doi

10.1016/j.ijpharm.2008.12.038

subject

Has Abstract

pub_date

2009-05-08 00:00:00

pages

33-8

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(08)00875-2

journal_volume

372

pub_type

杂志文章

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