An FDA approved neurokinin-1 receptor antagonist is effective in reducing intraabdominal adhesions when administered intraperitoneally, but not orally.
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.
Lim
Rizal
R
Department of Surgery, Boston University School of Medicine, 88 East Newton St. C500, Boston, MA 02118, USA.
Morrill
Jonathan M
JM
Prushik
Scott G
SG
Reed
Karen L
KL
Gower
Adam C
AC
Leeman
Susan E
SE
Stucchi
Arthur F
AF
Becker
James M
JM
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*
D000893:Anti-Inflammatory Agents; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D000077608:Aprepitant