Prevention of postsurgical peritoneal adhesion formation by intraperitoneal administration of ibuprofen

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 μg/10 μl/5 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 μg/kg/day. The minimum effective dose reported by this laboratory via systemic administration of ibuprofen for reduction of postsurgical peritoneal adhesions using a similar model was 35,000 μg/kg/day. 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.