betadex and hydrogen-sulfite

We examined the pharmacokinetics of edaravone when edaravone/hydroxypropyl-beta-cyclodextrin (HPbetaCD) complex solution, including L-cysteine (L-Cys) and sodium hydrogen sulfite (SHS), was administered intravenously, rectally and via the oral mucosa. In oral mucosal administration, atomized edaravone/HPbetaCD complex solution that contained L-Cys and SHS was sprayed into the mouth of Wistar rats. Oral mucosal and rectal administration of edaravone/HPbetaCD complex solution that contained L-Cys and SHS was compared with that for edaravone/HPbetaCD complex solution without L-Cys and SHS. When edaravone 0.25-1.0 mg was administered intravenously, C(0) and AUC(0-60) were linear. In oral mucosal and rectal administration, C(max) and AUC(0-60) of edaravone/HPbetaCD with L-Cys and SHS were significantly higher than those of edaravone/HPbetaCD without L-Cys and SHS. On the other hand, bioavailability of oral mucosal, rectal and oral administration was about 100, 63.5 and 26.6%, respectively. This study suggested that L-Cys and SHS were useful for the oral mucosal and rectal administration of edaravone.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Absorption; Administration, Oral; Administration, Rectal; Animals; Antipyrine; beta-Cyclodextrins; Cysteine; Edaravone; Male; Mouth Mucosa; Pharmaceutical Solutions; Rats; Rats, Wistar; Rectum; Sulfites