Lexipafant (BB-882), a platelet activating factor receptor antagonist, ameliorates mucosal inflammation in an animal model of colitis

Objective: To assess the anti-inflammatory action of lexipafant (BB-882), a platelet activating factor antagonist, in an animal model of acute colitis. Design: An animal intervention study. Methods: Following the rectal instillation of formalin 0.75% into male New Zealand White (NZW) rabbits, 0.85 mi of aggregated immunoglobulin was administered i.v. Treatment groups (0.8 mg/kg, n=6; 2.4 mg/kg, n=13; 3.2 mg/kg, n=10) were given bolus doses of BB-882 two-hourly i.v. (control group, n=25). Rectal dialysis was performed before induction of colitis and sacrifice. Dialysate leukotriene B-4 (LTB(4)), prostaglandin E(2) (PGE(2)) and thromboxane B-2 (TXB(2)) levels were determined. Tissue was saved for histology and measurement of myeloperoxidase content. Results: There was a dose-dependent improvement in macroscopic scores (2.4 and 3.2 mg/kg: P<0.02, P<0.001) and myeloperoxidase levels (3.2 mg/kg: P<0.04). Dialysate LTB(4) levels fell (2.4 and 3.2 mg/kg: P<0.03, P<0.02) as did PGE(2) levels. TXB(2) concentrations remained unaffected. Conclusion: The PAF receptor antagonist BB-882 shows efficacy in treating inflammation in an animal model of acute colitis as evidenced by a dose-dependent fall in macroscopic mucosal damage, neutrophil infiltration and reduced generation of inflammatory mediators.