Improvement of oral bioavailability of flurbiprofen from flurbiprofen/beta-cyclodextrin inclusion complex by action of cinnarizine.
Improvement of the oral bioavailability of flurbiprofen (Flu) after oral administration of flurbiprofen/beta-cyclodextrin inclusion complex (Flu/beta-CD) by the action of cinnarizine (CN) was investigated. Flu and Flu/beta-CD were administered orally to fasted rats at a dose of 20mg/kg as Flu. Thirty minutes after drug administration, CN dissolved in pH 4.0 buffer solution or pH 4.0 buffer solution alone was administered to the rats. The dose of CN was 0.17 mg/kg. Blood samples were taken from rats and Flu concentrations in plasma samples were determined by HPLC. It was found from the comparison of Flu and Flu with CN (Flu+CN) that CN had no effect on plasma concentrations of Flu after oral administration of Flu. The mean plasma levels after oral administration of Flu/beta-CD with CN (Flu/beta-CD+CN) were larger not only than those of Flu and Flu+CN but also than those of Flu/beta-CD. The value of C(max) in Flu/beta-CD+CN was significantly larger than that of Flu/beta-CD. This is considered to be caused by the action of CN as a competing agent. This mechanism was supported by the result of solubility study in which Flu solubility in beta-CD solution decreased with the addition of CN. It was found from these results that CN had strong ability as a competing agent in vivo.
Tokumura
Tadakazu
T
Department of Drug Delivery Research, Hoshi University, Shinagawa, Tokyo, Japan. tokumura@pep.ne.jp
Muraoka
Atsushi
A
Machida
Yoshiharu
Y
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002936:Cinnarizine / Q000008:administration & dosage / Q000378:metabolism*; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods*; D004347:Drug Interactions / Q000502:physiology; D005480:Flurbiprofen / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000378:metabolism*
D004338:Drug Combinations; D047392:beta-Cyclodextrins; D002936:Cinnarizine; D005480:Flurbiprofen; C031215:betadex