Actions of glucocorticoids to antagonise cisplatin-induced acute and delayed emesis in ferret

Cisplatin 5 mg/kg, i.p. induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the potential anti-emetic activity of several glucocorticoids. Betamethasone (0.3–3 mg/kg, i.p.) reduced the emesis occurring during the initial 0–24-h period by 71.1–99.5% (P0.05). However, all glucocorticoids dose-dependently reduced retching+vomiting during the subsequent 24–56-h period. The rank order of anti-emetic potency was betamethasone (ID80methylprednisolone (ID80=0.66 mg/kg)≫hydrocortisone (ID80\u3e30 mg/kg). Dexamethasone was ineffective to antagonise the retching+vomiting response during the 24–56-h period when the administration was delayed until 24 h post-cisplatin injection. None of the glucocorticoids reduced the retching+vomiting response occurring during the 56–72-h period. In conclusion, the rank order of anti-emetic potency suggests that inflammation, or mediators of inflammation, contribute to the retching+vomiting response induced by cisplatin