Comparative effects of pirfenidone and nintedanib in experimental intraabdominal adhesion model

Abstract

Background: Postoperative peritoneal adhesions (PPA) develop in up to 90% of intraabdominal surgeries and are a major cause of small bowel obstruction, leading to readmissions and morbidity. However, no effective pharmacologic strategy currently exists for PPA prevention. Pirfenidone and Nintedanib are oral antifibrotics approved for idiopathic pulmonary fibrosis, with emerging data on their effects in cardiac and hepatic fibrosis. This study aimed to compare their efficacy in preventing PPA via intraperitoneal (IP) administration in an experimental model. Methods: Twenty-eight rats were randomized into four groups of 7: Pirfenidone (P), Nintedanib (N), combination (P + N), and saline control (C). Adhesions were induced via cecal abrasion. On postoperative day 7, macroscopic fibrosis scores (MFS), affected regions, histopathology, and TGF-beta 1 expression were evaluated. Results: Group P had significantly lower MFS than Group N (P < 0.001) and showed a reduction trend vs. control. TGF-beta 1 HScore was significantly lower in Group P vs. Group N (P = 0.002) and P + N (P = 0.014). Group N showed the highest inflammation and elevated TGF-beta 1 vs. control (P = 0.013). Conclusion: Pirfenidone appears effective in reducing PPA formation via IP administration. In contrast, Nintedanib may be unsuitable for IP use in saline, potentially due to poor solubility.