EFFECTS OF GRANISETRON AND ITS COMBINATION WITH DEXAMETHASONE ON CISPLATIN-INDUCED DELAYED EMESIS IN THE FERRET

1. Granisetron and its combination with dexamethasone for the treatmen t of delayed emesis following cisplatin (CDDP) administration were inv estigated using ferrets. 2. CDDP-induced emesis was significantly inhi bited in both the granisetron group and the combined granisetron and d examethasone group during the acute and delayed phase in terms of tota l emesis, latency to first emesis and duration of emesis. 3. Food and water consumption in the combined group of ferrets was significantly i ncreased as compared with the CDDP control group. 4. 5-Hydroxytryptami ne (5-HT) level was increased in the ileum and the 5-hydroxyindole ace tic acid (5-HIAA) level was increased in the area postrema of ferrets after 3 days of CDDP administration. It is suggested that the antiemet ic activity of granisetron and/or dexamethasone is not related to 5-HT levels in delayed emesis. 5. Both granisetron and its combination wit h dexamethasone are effective in CDDP-induced emesis, but combination treatment is more effective than granisetron alone for the duration of emesis in the delayed phase. (C) 1998 Elsevier Science Inc.