Ondansetron and Granisetron in the Prophylaxis of Nausea and Emesis Induced by Cisplatin in Dogs

Topal A. , M. Kaya, N. Gül: Ondansetron and Granisetron in the Prophylaxis of Nausea and Emesis Induced by Cisplatin in Dogs. Acta Vet. Brno 2005, 74: 111-116. In the present study, the effects of 5-HT3 receptor antagonist granisetron and ondansetron on the acute phase of cisplatin-induced nausea and emesis were analyzed in dogs. Fifteen healty dogs were used in this study. Cisplatin was administrated to all dogs to induce nausea and vomiting. All dogs that received cisplatin (3 mg/kg IV) were observed continuously for 8 h. Five dogs administered only cisplatin acted as controls. Cisplatin induced emetic response and nausea was detected in the controls. Ondansetron (1 mg/kg IV) and granisetron (60 μg/kg IV) were administered to the other animals 30 min. before cisplatin administration. Although acute vomiting was significantly inhibited by ondansetron and granisetron, granisetron was found more effective on the nausea. It was concluded that both ondansetron and granisetron are effective in the control of cisplatininduced vomiting in dogs, but granisetron is more effective than ondansetron in the inhibition of cisplatin-induced nausea in dogs. 5-HT3 receptor antagonist, vomiting, emetic response, canine Highly emetogenic chemotheraputic agents, including cisplatin, are widely used in treating malignant disease with the most feared side effects occurring as nausea and vomiting (Laszlo and Lucas 1981; Jones et al.1991; Fukui et al. 1999; Tanihata et al. 2000; Goodin and Cunningham 2002; Schnel l 2003 ). Nausea and vomiting associated with chemotherapy can be classified as acute, delayed or anticipatory. Acute nausea and vomiting are defined as occurring within 24 h after chemotherapy and can be subdivided into acute (within12 h) and late-acute (12 24 h) in humans (Schnel l 2003). Although the extent of nausea and vomiting varies by chemotherapeutic regimen, more than 90% of patients who receive ≥ 50 mg/m2 of cisplatin will vomit during the first 24 h after administration unless they receive effective prophylactic antiemetic therapy (Spector et al.1998; Schnel l et al. 2003). In a previous experimental study (Fukui et al. 1999) it has been reported that cisplatin at a non-lethal dose (3 mg/kg, iv) induced acute phase vomiting in dogs, up to around 3 h after administration. This study also showed that cisplatin may not cause delayed emesis in dogs. The 5-HT3 receptor antagonists have been regarded as the ‘gold standard’ in antiemetic therapy. Numerous studies investigating the use of ondansetron and granisetron have shown that when delivered intravenously both drugs are safe and highly effective in preventing nausea and vomiting induced by moderately high or highly emetogenic chemotherapy in humans (Spector et al. 1998; Fox-Geiman et al. 2001; Goodin and Cunningham 2002). Although both ondansetron and granisetron exhibit high binding affinities for the 5HT3 receptor, ondansetron also possesses weak affinity for 5-HT1B, 5-HT1C, α-adrenergic and μ-opioid receptors in humans. On the other hand, granisetron possesses significantly longer elimination half-lives than ondansetron (Goodin and Cunningham 2002; Navari 2003; Schnel l 2003). ACTA VET. BRNO 2005, 74: 111-116 Address for correspondence: A. Topal Department of Surgery Faculty of Veterinary Medicine Uludag University 16190 Bursa, TURKEY Phone: + 90 224 2347655 Fax: + 90 224 2346395 E-mail: [email protected] http://www.vfu.cz/acta-vet/actavet.htm