• Brigitte M Richard, Laura R Ott, Dean Haan, Abram N Brubaker, Phaedra I Cole, Keith G Nelson, Paul E Ross, Marlon C Rebelatto, and Paul E Newton.
• Clinical Research & Drug Safety Assessment, Pacira Pharmaceuticals, Inc., San Diego, CA 92121, USA. brigitter@pacira.com
• Expert Opin Investig Drugs. 2011 Oct 1;20(10):1327-41.

ObjectiveDepoFoam bupivacaine (DB) is in development for prolonged postoperative analgesia. Studies were conducted to evaluate the potential local and systemic toxicity and any effect on wound healing after wound infiltration.MethodsThe model simulates an inguinal hernia (skin incision ∼2.5 and 5.5 cm). Animals (four/sex/group of each species) received DB 9, 18 or either 25 or 30 mg/kg, bupivacaine solution (B(sol); 7.5 mg/ml, 9 mg/kg) or saline. DB was given at 0.6, 1.2 and 1.0 or 1.2 ml/kg, respectively, and B(sol) or saline at 1.2 ml/kg. Each dose was infiltrated in small fractions on Day 1. End points included histology on Days 3 and 15. Wound healing was recorded on Day 2 through Day 15.ResultsThere was no adverse effect in either species. Notably, granulomatous inflammation was noted in surgical sites from 8 of 24 rabbits in the DB groups only. Based on the minimal to mild severity on Day 15, this was considered a normal reaction against the liposomes. Except for granulomatous inflammation, there were no differences in overall incidence or severity of histologic changes in the sites dosed to DB, saline or B(sol).ConclusionsThe data reported here are the first demonstration of the safety of DB in toxicology species.

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