The interaction of dexamethasone with ondansetron on drug-induced emesis in the ferret

The potential of dexamethasone (0.5-20 mg/kg i.p.) to antagonize the emesis induced by cisplatin (10 mg/kg i.v.), apomorphine (0.25 mg/kg s.c.), morphine (0.5 mg/kg s.c.) and copper sulphate (100 mg/kg intragastric) was investigated alone and in combination with ondansetron in the ferret. There was a trend for dexamethasone 0.1-5 mg/kg to reduce cisplatin-induced emesis and for 0.05-2.5 mg/kg to delay the onset of apomorphine-induced emesis but doses of dexamethasone up to 20 mg/kg were without effect to modify morphine- or copper sulphate-induced emesis. The combination of dexamethasone 2.5 mg/kg with ondansetron 0.1 mg/kg did not have additive effects to reduce cisplatin-induced emesis but did reduce significantly the total numbers of episodes recorded. Ondansetron 1 mg/kg was without effect to modify apomorphine-, morphine- or copper sulphate-induced emesis but the combination pretreatment of ondansetron 1 mg/kg with dexamethasone 2.5 and 5 mg/kg reduced significantly apomorphine-induced retching. Data are discussed in terms of the antiemetic effectiveness of dexamethasone to antagonize chemotherapy-induced emesis in man.