The inclusion of fluoxetine into gamma-cyclodextrin increases its bioavailability: behavioural, electrophysiological and pharmacokinetic studies

The inclusion of a drug into cyclodextrin generally results in the modifica tion of its physical and chemical properties and sometimes can increase its oral bioavailability. The aim of this study was to compare the effects of the fluoxetine HCl/gamma-cyclodextrin complex to that of traditional fluoxe tine HCl. In the forced swimming test in mice, fIuoxetine HCl/gamma-cyclode xtrin was more effective than fluoxetine HCl, the ED(30)s being, respective ly, 9.5 and 26.9 mg/kg PO. Both compounds (10 mg/kg PO) were able to reduce the tiring rate of dorsal raphe neurons in the rat. However, between-group s comparisons showed no significant differences between fluoxetine HCl trea ted animals and the vehicle group, while fluoxetine HCl/gamma-cyclodextrin appeared significantly more effective than vehicle from minute 25 of the me asurement period. In healthy volunteers, the relative oral bioavailability, calculated as the ratio AUC 0-infinity fluoxetine HCl/gamma-cyclodextrin o n AUC 0-infinity fluoxetine HCl (20 mg PO), was equal to 249.9%. The three experiments taken together suggest that the complexation of fluoxetine HCl into gamma-cyclodextrin increases its pharmacological. efficacy in animals, this effect being related to an enhancement of its oral bioavailability as demonstrated in human healthy subjects.