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01.10.2008 | ssat plenary presentation

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

verfasst von: Rizal Lim, Jonathan M. Morrill, Scott G. Prushik, Karen L. Reed, Adam C. Gower, Susan E. Leeman, Arthur F. Stucchi, James M. Becker

Erschienen in: Journal of Gastrointestinal Surgery | Ausgabe 10/2008

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Abstract

Introduction

Postoperative 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.

Methods

Adhesions 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.

Results

IP 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.

Conclusion

These data suggest that aprepitant maybe a useful pharmacologic agent for reducing adhesion formation clinically.

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Titel: An FDA Approved Neurokinin-1 Receptor Antagonist is Effective in Reducing Intraabdominal Adhesions when Administered Intraperitoneally, But Not Orally
verfasst von: Rizal Lim
Jonathan M. Morrill
Scott G. Prushik
Karen L. Reed
Adam C. Gower
Susan E. Leeman
Arthur F. Stucchi
James M. Becker
Publikationsdatum: 01.10.2008
Verlag: Springer-Verlag
Erschienen in: Journal of Gastrointestinal Surgery / Ausgabe 10/2008
Print ISSN: 1091-255X
Elektronische ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-008-0634-4

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Abstract

Introduction

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Conclusion

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