Abstract
The antiemetic activity of granisetron was examined in ferrets aged 10-13 weeks. Emesis was induced by exposure to either whole-body X-irradiation (50 Gy over 10.4 min) or cyclophosphamide (80 mg/kg i.v.) plus doxorubicin (6 mg/kg i.v.). Following exposure to whole-body X-irradiation, the young ferrets vomited with a similar latency to vomit and severity of emesis to that shown by adult animals. Granisetron (0.5 mg/kg i.v.) significantly reduced (P < or = 0.05) the number of vomits and retches and two out of four animals were completely protected. Following injection of cyclophosphamide and doxorubicin, the young ferrets showed a reduced emetic response compared to adult animals. Following a dose of granisetron (0.5 mg/kg i.v.), only one out of four ferrets vomited compared to four out of four in the control group. Further experiments showed that cisplatin (12.5 mg/kg i.v.) was unable to induce vomiting in the young ferret (n = 2). Granisetron (0.5 mg/kg i.v.) was well tolerated by the young ferret and was able to reduce significantly or completely abolish emesis induced by cytostatic treatment. The data support the use of granisetron in pediatric patients and clinical trials are currently underway in this patient population.