Marr H E, Davey P T, Boyle E A, Blower P R
SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
J Cancer Res Clin Oncol. 1994;120(4):204-7. doi: 10.1007/BF01372557.
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.
在10 - 13周龄的雪貂身上研究了格拉司琼的止吐活性。通过全身X射线照射(10.4分钟内50 Gy)或环磷酰胺(80 mg/kg静脉注射)加阿霉素(6 mg/kg静脉注射)诱导呕吐。全身X射线照射后,幼龄雪貂呕吐的潜伏期和呕吐严重程度与成年动物相似。格拉司琼(0.5 mg/kg静脉注射)显著减少(P≤0.05)呕吐和干呕次数,4只动物中有2只得到完全保护。注射环磷酰胺和阿霉素后,幼龄雪貂的呕吐反应比成年动物减少。给予一剂格拉司琼(0.5 mg/kg静脉注射)后,4只雪貂中只有1只呕吐,而对照组4只均呕吐。进一步实验表明,顺铂(12.5 mg/kg静脉注射)不能诱导幼龄雪貂(n = 2)呕吐。幼龄雪貂对格拉司琼(0.5 mg/kg静脉注射)耐受性良好,并且能够显著减少或完全消除细胞毒性治疗引起的呕吐。这些数据支持格拉司琼在儿科患者中的应用,目前正在该患者群体中进行临床试验。