An FDA Approved Neurokinin-1 Receptor Antagonist is Effective in Reducing Intraabdominal Adhesions when Administered Intraperitoneally, But Not Orally

Abstract

IntroductionPostoperative adhesions pose a continued healthcare problem. We previously demonstrated that intraperitoneal (IP) 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 IP and oral administration of aprepitant on adhesion formation in a rat model. MethodsAdhesions were surgically induced in rats that were randomized to receive either one or five oral preoperative doses or a single intraoperative IP dose of aprepitant (50 mg/kg). Adhesions were scored at 7 days. In similar experiments using IP 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. ResultsIP aprepitant reduced adhesion formation by 33% (p < 0.05) compared with controls while oral aprepitant had no effect. Compared to controls IP aprepitant reduced tPA activity by 55% (p < 0.05), increased PAI-1 mRNA levels by 140% (p < 0.05), and had no affect on tPA mRNA levels. ConclusionThese data suggest that aprepitant maybe a useful pharmacologic agent for reducing adhesion formation clinically.