Marr H E, Davey P T, Boyle E A, Blower P R
SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
Pharmacology. 1994 May;48(5):283-92. doi: 10.1159/000139191.
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.
在雪貂中，高选择性5-羟色胺3受体拮抗剂格拉司琼，通过多种途径（静脉内、口服、皮下、肌肉内）给药时，能以剂量依赖的方式消除或减少顺铂（10毫克/千克静脉注射）或全身X射线照射（10.4分钟内50戈瑞）诱导的呕吐。静脉注射或口服0.5毫克/千克格拉司琼可完全防止呕吐和干呕。在顺铂给药前6小时给予格拉司琼（0.5毫克/千克静脉注射）也有效，能使50%的雪貂在总共10小时内得到完全保护。重复给药后，即在催吐刺激前静脉注射4天或口服10天，格拉司琼（0.5毫克/千克）在第5天或第11天仍保留其止吐活性。预先用环磷酰胺（80毫克/千克静脉注射）治疗会使暴露于X射线照射后呕吐发作的时间显著缩短。在这种联合催吐方案后作为干预措施给予格拉司琼而非生理盐水时，可消除呕吐和恶心。这些结果表明，格拉司琼通过多种不同途径给药具有潜在的灵活性，并且在用作针对多种细胞毒性药物的止吐药时作用持续时间长。
