Substance P (neurokinin-1) antagonist prevents postoperative vomiting after abdominal hysterectomy procedures

Background: The safety and antiemetic efficacy of CP-122, 721, a novel neur okinin-1 antagonist, was evaluated when administered alone or in combinatio n with ondansetron. Methods: Using a randomized, double-blind, placebo-controlled study design, CP-122,721 was initially compared with placebo and subsequently to ondanse tron alone and in combination for prophylaxis against postoperative nausea and vomiting in 243 women undergoing abdominal hysterectomy. In the dose-ra nging studies (n = 86), patients received either CP-122,721 100 mg Cvs. pla cebo) or 200 mg (vs. placebo) orally 60-90 min before induction of anesthes ia. In the interaction study (n = 157), patients received CP-122,721 200 mg or placebo 60-30 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 ca re unit and at 0.5-, 1-, 1.5-, 2-, 4-, 8-, 12-, and 24-h intervals postoper atively. Emetic episodes, need for rescue antiemetic-antinausea medication, postoperative complications, and patient satisfaction were recorded. Results: In the initial dose-ranging study, only 10% of the patients experi enced emesis within the first 8 h after surgery with CP-122,721 200 mg comp ared with 50% in the placebo group. CP-122,721 200 mg also decreased the ne ed 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 oral ly experienced emesis less than 2 h after surgery compared with 17% with on dansetron alone. With combined therapy, only 2% experienced emesis. In addi tion, the median times for 75% of patients to remain free from postoperativ e nausea and vomiting were 82, 75, and 362 min in the ondansetron, CP-122,7 21, and combination groups, respectively. Conclusions: Oral CP-122,721 200 mg decreased emetic episodes compared with ondansetron (4 mg intravenously) during the first 24 h after gynecologic s urgery; however, there was no difference in patient satisfaction.