Substance P (Neurokinin-1) antagonist prevents postoperative vomiting after abdominal hysterectomy procedures.
BACKGROUND
The safety and antiemetic efficacy of CP-122,721, a novel neurokinin-1 antagonist, was evaluated when administered alone or in combination with ondansetron.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gesztesi
Z
Z
Departments of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Scuderi
P E
PE
White
P F
PF
Wright
W
W
Wender
R H
RH
D'Angelo
R
R
Black
L S
LS
Dalby
P L
PL
MacLean
D
D
D000284:Administration, Oral; D000328:Adult; D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects* / Q000379:methods; D007275:Injections, Intravenous; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control*; D011229:Preanesthetic Medication; D012307:Risk Factors; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013373:Substance P / Q000037:antagonists & inhibitors*
D000932:Antiemetics; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D010919:Placebos; D012702:Serotonin Antagonists; D013373:Substance P; D017294:Ondansetron; C099414:(2S,3S)-2-phenyl-3-((5-trifluoromethoxy-2-methoxy)benzylamino)piperidine