Methotrexate produces delayed emesis in dogs: a potential model of delayed emesis induced by chemotherapy

We investigated the emetic effects of cisplatin and methotrexate in dogs, the effects of ondansetron on cisplatin-induced vomiting, and the effects of ondansetron, dexamethasone and a combination of the two on the vomiting induced by methotrexate. Ondansetron was administered 30 min before cisplatin administration. Ondansetron, dexamethasone or a combination of the two was administered 8, 24 and 48 h after methotrexate administration. Cisplatin (3 mg/kg, i.v.) induced acute vomiting but failed to induce delayed vomiting. The acute Vomiting was markedly inhibited by ondansetron (3 mg/kg, p.o.; 1 mg/kg, i.v.). Methotrexate (2.5 mg/kg, i.v.) caused delayed vomiting, which was partly inhibited by ondansetron (1 mg/kg, i.v.) or dexamethasone (2.5 mg/kg, i.v.). The combination of the two agents was more effective. These results suggest that methotrexate-induced emesis in dogs would be useful for studying delayed emesis. (C) 1999 Elsevier Science B.V. All rights reserved.