Gesztesi Z, Scuderi P E, White P F, Wright W, Wender R H, D'Angelo R, Black L S, Dalby P L, MacLean D
Departments of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Anesthesiology. 2000 Oct;93(4):931-7. doi: 10.1097/00000542-200010000-00009.
The safety and antiemetic efficacy of CP-122,721, a novel neurokinin-1 antagonist, was evaluated when administered alone or in combination with ondansetron.
Using a randomized, double-blind, placebo-controlled study design, CP-122,721 was initially compared with placebo and subsequently to ondansetron alone and in combination for prophylaxis against postoperative nausea and vomiting in 243 women undergoing abdominal hysterectomy. In the dose-ranging studies (n = 86), patients received either CP-122,721 100 mg (vs. placebo) or 200 mg (vs. placebo) orally 60-90 min before induction of anesthesia. In the interaction study (n = 157), patients received CP-122,721 200 mg or placebo 60-90 min before induction of anesthesia, and ondansetron 4 mg or saline 2 ml intravenously 15-30 min before the end of surgery. Patients assessed their level of nausea and pain on arrival in the postanesthesia care unit and at 0.5-, 1-, 1.5-, 2-, 4-, 8-, 12-, and 24-h intervals postoperatively. Emetic episodes, need for rescue antiemetic-antinausea medication, postoperative complications, and patient satisfaction were recorded.
In the initial dose-ranging study, only 10% of the patients experienced emesis within the first 8 h after surgery with CP-122,721 200 mg compared with 50% in the placebo group. CP-122,721 200 mg also decreased the need for rescue medication (25% vs. 48%). CP-122,721 100 mg was less effective than 200 mg in decreasing the incidence of repeated episodes of emesis. In the interaction study, 6% of the patients receiving CP-122,721 200 mg orally experienced emesis less than 2 h after surgery compared with 17% with ondansetron alone. With combined therapy, only 2% experienced emesis. In addition, the median times for 75% of patients to remain free from postoperative nausea and vomiting were 82, 75, and 362 min in the ondansetron, CP-122,721, and combination groups, respectively.
Oral CP-122,721 200 mg decreased emetic episodes compared with ondansetron (4 mg intravenously) during the first 24 h after gynecologic surgery; however, there was no difference in patient satisfaction.
评估新型神经激肽-1拮抗剂CP-122,721单独使用或与昂丹司琼联合使用时的安全性和止吐疗效。
采用随机、双盲、安慰剂对照研究设计，最初将CP-122,721与安慰剂进行比较，随后再将其与单独使用及联合使用的昂丹司琼进行比较，以预防243例行腹部子宫切除术的女性术后恶心和呕吐。在剂量范围研究（n = 86）中，患者在麻醉诱导前60 - 90分钟口服CP-122,721 100毫克（与安慰剂对比）或200毫克（与安慰剂对比）。在相互作用研究（n = 157）中，患者在麻醉诱导前60 - 90分钟接受CP-122,721 200毫克或安慰剂，在手术结束前15 - 30分钟静脉注射昂丹司琼4毫克或生理盐水2毫升。患者在到达麻醉后护理单元时以及术后0.5、1、1.5、2、4、8、12和24小时评估其恶心和疼痛程度。记录呕吐发作情况、使用急救止吐抗恶心药物的需求、术后并发症及患者满意度。
在初始剂量范围研究中，CP-122,721 200毫克组在术后最初8小时内仅有10%的患者出现呕吐，而安慰剂组为50%。CP-122,721 200毫克组也减少了急救药物的使用需求（25%对48%）。CP-122,721 100毫克在降低反复呕吐发作发生率方面不如200毫克有效。在相互作用研究中，口服CP-122,721 200毫克的患者中有6%在术后不到2小时出现呕吐，而单独使用昂丹司琼组为17%。联合治疗时，仅有2%的患者出现呕吐。此外，昂丹司琼组、CP-122,721组和联合治疗组中75%的患者术后无恶心和呕吐的中位时间分别为82分钟、75分钟和362分钟。
在妇科手术后的最初24小时内，口服CP-122,721 200毫克与静脉注射昂丹司琼（4毫克）相比，呕吐发作次数减少；然而，患者满意度无差异。
