Prevention of postsurgical peritoneal adhesion formation by intraperitoneal administration of ibuprofen

Abstract

Orita, H., W. Girgis, and G.S. diZerega: Prevention of postsurgical peritoneal adhesion formation by intraperitoneal administration of ibuprofen. Drug Dev. Res. 10:97-105, 1987.Previously, we reported a reduction in the formation of post-surgical peritoneal adhesions accompanying the use of systemically administered ibuprofen in validated animal models. Since the use of systemic ibuprofen requires high doses, we evaluated intraperitoneal drug delivery to assess the effects of locally administered low doses of ibuprofen on adhesion formation. Adhesion formation was evaluated after (a) parietal peritoneal excision, (b) abrasion of large bowel serosal, and (c) both (a + b) performed together.Adhesions formed in 2/15 rabbits with parietal peritoneal excision only, 3/15 with serosal abrasion only, and 11/15 with both procedures performed in the same rabbit. To further validate the parietal peritoneal excision + adjacent serosal abrasion technique for adhesion induction, a second group of 23 rabbits was similarly treated; 20/23 were found to have adhesions. The minimum dose of ibuprofen delivered into the intraperitoneal cavity via Alzet pump which reduced adhesions was 5 pg/lO pV15 cm2 test site/hr. No more than 4-5 days of postoperative treatment were required to achieve a significant reduction in adhesion formation. In the 2-kg rabbits used here that would provide a total daily dose of 60 pg/kg/day. The minimum effective dose reported by this laboratory via systemic administration of ibuprofen for reduction of postsurgical peritoneal adhesions using a similar 98Orita, Girgis, and diZerega model was 35,000 pglkglday. The potential utility of these findings is enhanced by the ongoing development of biodegradable drug delivery systems which can administer ibuprofen within the peritoneal cavity.

Update on antiadhesion barriers and therapeutics in gynecological surgery

“…Nonsteroidal anti-inflammatory drugs have been shown to reduce peritoneal adhesions in many animal models [53][54][55]. They act by decreasing prostaglandin and thromboxane synthesis causing decreased vascular permeability, platelet aggregation and clot formation.…”

Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies

“…Administration of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to decrease peritoneal, pelvic, and tendon adhesions in rabbit, hamster, guinea pig, and porcine models [164][165][166][167][168][169][170][171][172][173][174][175][176]. Although the exact mechanism by which they exert this effect is unclear, it is likely secondary to their inhibition of cyclooxygenase 2 (COX-2), which leads to decreased production of prostaglandins in the inflammatory cascade [177].…”

Comparative studies of thermogels in preventing post-operative adhesions and corresponding mechanisms

“…Over recent decades, numerous pharmacological and barrier-based approaches have been tried to prevent post-operative adhesions. [5][6][7][8] Barrier systems in the form of polymer solutions or solid membranes are currently one of the most effective approaches for reducing adhesion formation. [9][10][11][12] They separate the injured regions during the critical period of adhesion development 3-5 days after surgery.…”