FURTHER-STUDIES OF THE ANTIEMETIC ACTIVITY OF GRANISETRON AGAINST WHOLE-BODY X-IRRADIATION OR CISPLATIN-INDUCED EMESIS IN THE FERRET

In ferrets, the highly selective 5-HT3 receptor antagonist, granisetro n, abolished or reduced emesis induced by cisplatin (10 mg/kg i.v.) or whole body X-irradiation (50 Gy in 10.4 min) in a dose-dependent mann er when administered by a variety of routes (intravenous, per os, subc utaneous, intramuscular). Complete protection from vomiting and retchi ng was achieved with 0.5 mg/kg i.v. or p.o. granisetron. Granisetron ( 0.5 mg/kg i.v.) was also effective when given 6 h before cisplatin, co mpletely protecting 50% of ferrets for a total of 10 h. Following repe at dosing, for either 4 days i.v. or 10 days p.o. before emetic challe nge, granisetron (0.5 mg/kg) still retained its antiemetic activity on the 5th or 11th day. Prior treatment with cyclophosphamide (80 mg/kg i.v.) resulted in a significantly shorter time to the onset of vomitin g after exposure to X-irradiation. Granisetron, but not saline, abolis hed vomiting and nausea when given as intervention after this combined emetic regimen. These results show that granisetron has potential fle xibility for administraton via a variety of different routes and also a long duration of action when used as an antiemetic against a wide ra nge of cytostatic agents.