title: An FDA approved neurokinin-1 receptor antagonist is effective in reducing intraabdominal adhesions when administered intraperitoneally, but not orally.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 no affect on tPA mRNA levels.
  
  
  CONCLUSIONS
  These data suggest that aprepitant maybe a useful pharmacologic agent for reducing adhesion formation clinically.
authors: Department of Surgery, Boston University School of Medicine, 88 East Newton St. C500, Boston, MA 02118, USA.
authors: Rizal
authors: R
authors: Lim
authors: Jonathan M
authors: JM
authors: Morrill
authors: Scott G
authors: SG
authors: Prushik
authors: Karen L
authors: KL
authors: Reed
authors: Adam C
authors: AC
authors: Gower
authors: Susan E
authors: SE
authors: Leeman
authors: Arthur F
authors: AF
authors: Stucchi
authors: James M
authors: JM
authors: Becker
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000077608:Aprepitant; D004195:Disease Models, Animal; D007263:Infusions, Parenteral; D009025:Morpholines / Q000008:administration & dosage*; D064729:Neurokinin-1 Receptor Antagonists; D010532:Peritoneal Diseases / Q000517:prevention & control*; D051381:Rats; D000267:Tissue Adhesions / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D000077608:Aprepitant