Improvement of oral bioavailability of flurbiprofen from flurbiprofen/β-cyclodextrin inclusion complex by action of cinnarizine

Improvement of the oral bioavailability of flurbiprofen (Flu) after oral administration of flurbiprofen/β-cyclodextrin inclusion complex (Flu/β-CD) by the action of cinnarizine (CN) was investigated. Flu and Flu/β-CD were administered orally to fasted rats at a dose of 20 mg/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/β-CD with CN (Flu/β-CD + CN) were larger not only than those of Flu and Flu + CN but also than those of Flu/β-CD. The value of C_max in Flu/β-CD + CN was significantly larger than that of Flu/β-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 β-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.