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.
Drug Safety Research Laboratories, Takeda Chemical Industries, Osaka, japan.
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H
Fukui
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Yamamoto
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D017294:Ondansetron / Q000494:pharmacology*; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control
D000932:Antiemetics; D000970:Antineoplastic Agents; D017294:Ondansetron; D003907:Dexamethasone; D002945:Cisplatin; D008727:Methotrexate