In a ferret-model of Cisplatin- induced emesis, Casopitant (GW679769) inhibits retching and vomiting and reduced nausea-like behaviours in a dose-dependent manner. The pharmacokinetics and brain penetration of casopitant are studied in the ferret-model of cisplatin-induced emesis. Following a single intraperitoneal dose, radioactive labeled Casopitant ([14C]Casopitant) is rapidly absorbed, with plasma and brain concentrations being approximately equal at two hours post-dosing. [14C]Casopitant is found in the brain as the parent compound and two major oxidative metabolites (M1 and M2), accounting for approximately 76%, 19%, and 3% of the radioactivity, respectively; suggesting that the pharmacologic activity of Casopitant in the ferret is largely attributable to the parent compound. Casopitant possesses a high affinity for brain NK1 receptors in the ferret[2].
