A novel administration route of edaravone--II: mucosal absorption of edaravone from edaravone/hydroxypropyl-beta-cyclodextrin complex solution including L-cysteine and sodium 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.
Sato
Toshiaki
T
Research and Development Division, Mikasa Seiyaku Co Ltd, Tokyo, Japan.
Mizuno
Keizo
K
Ishii
Fumiyoshi
F
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000042:Absorption / Q000187:drug effects / Q000502:physiology; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003545:Cysteine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077553:Edaravone; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D013447:Sulfites / Q000008:administration & dosage / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D019999:Pharmaceutical Solutions; D013447:Sulfites; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003545:Cysteine; C042345:hydrogen sulfite; D000077553:Edaravone; D000983:Antipyrine; C025026:sodium sulfite