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, granisetron, 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 manner when administered by a variety of routes (intravenous, per os, subcutaneous, intramuscular). Complete protection from vomiting and retching 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, completely protecting 50% of ferrets for a total of 10 h. Following repeat dosing, for either 4 days i.v. or 10 days p.o. before emetic challenge, 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 vomiting after exposure to X-irradiation. Granisetron, but not saline, abolished vomiting and nausea when given as intervention after this combined emetic regimen. These results show that granisetron has potential flexibility for administration via a variety of different routes and also a long duration of action when used as an antiemetic against a wide range of cytostatic agents.
SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
H E
HE
Marr
P T
PT
Davey
E A
EA
Boyle
P R
PR
Blower
D000818:Animals; D002945:Cisplatin; D004305:Dose-Response Relationship, Drug; D005260:Female; D005289:Ferrets; D017829:Granisetron / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D011292:Premedication; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D014916:Whole-Body Irradiation
D002945:Cisplatin; D017829:Granisetron