(2s-3s)-2-phenyl-3-((5-trifluoromethoxy-2-methoxy)benzylamino)piperidine and Postoperative-Nausea-and-Vomiting

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.

Topics: Administration, Oral; Adult; Antiemetics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hysterectomy; Injections, Intravenous; Neurokinin-1 Receptor Antagonists; Ondansetron; Piperidines; Placebos; Postoperative Nausea and Vomiting; Preanesthetic Medication; Risk Factors; Serotonin Antagonists; Substance P