An FDA approved neurokinin-1 receptor antagonist is effective in reducing intraabdominal adhesions when administered intraperitoneally, but not orally.

Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract
Rizal LimJ M Becker

Abstract

Postoperative adhesions pose a continued healthcare problem. We previously demonstrated that intraperitoneal (i.p.) administration of a neurokinin-1 receptor antagonist (NK-1RA) at surgery reduces intraabdominal adhesions in rats. The NK-1RA aprepitant (Emend, Merck) is clinically approved for preventing postoperative nausea and vomiting; however, its effects on adhesion formation are unknown. Thus, we determined the effects of i.p. and oral administration of aprepitant on adhesion formation in a rat model. Adhesions were surgically induced in rats that were randomized to receive either one or five oral preoperative doses or a single intraoperative i.p. dose of aprepitant (50 mg/kg). Adhesions were scored at 7 days. In similar experiments using i.p. dosing, animals were sacrificed at 24 h and peritoneal fluid, and tissue were collected to assess fibrinolytic activity and tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) mRNA levels, respectively. I.p. aprepitant reduced adhesion formation by 33% (p < 0.05) compared with controls while oral aprepitant had no effect. Compared to controls i.p. aprepitant reduced tPA activity by 55% (p < 0.05), increased PAI-1 mRNA levels by 140% (p < 0.05), and had n...Continue Reading

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Citations

Feb 3, 2012·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·Christoph BrochhausenC James Kirkpatrick
May 21, 2009·British Journal of Anaesthesia·P DiemunschJ-F Brichant
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May 20, 2014·The Journal of Surgical Research·Michael R CassidyArthur F Stucchi
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Dec 23, 2016·The Journal of Craniofacial Surgery·Rizal Lim
Dec 29, 2009·The Journal of Surgical Research·Brian C Ward, Alyssa Panitch

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