The Safety of EXPAREL Ⓡ (Bupivacaine Liposome Injectable Suspension) Administered by Peripheral Nerve Block in Rabbits and Dogs

• Published in: Journal of Drug Delivery 2012-01, Vol.2012, p.398-407
• Main Authors: Richard, Brigitte M., Newton, Paul, Ott, Laura R., Haan, Dean, Brubaker, Abram N., Cole, Phaedra I., Ross, Paul E., Rebelatto, Marlon C., Nelson, Keith G.
• Format: Article
• Language: English
• ISSN: 2090-3014; 2090-3022
• DOI: 10.1155/2012/962101

A sustained-release DepoFoam injection formulation of bupivacaine (EXPAREL, 15 mg/mL) is currently being investigated for postsurgical analgesia via peripheral nerve block (PNB). Single-dose toxicology studies of EXPAREL (9, 18, and 30 mg/kg), bupivacaine solution (Bsol, 9 mg/kg), and saline injected around the brachial plexus nerve bundle were performed in rabbits and dogs. The endpoints included clinical pathology, pharmacokinetics, and histopathology evaluation on Day 3 and Day 15 (2/sex/group/period). EXPAREL resulted in a nearly 4-fold lower Cmax versus Bsol at the same dose. EXPAREL was well tolerated at doses up to 30 mg/kg. The only EXPAREL-related effect seen was minimal to mild granulomatous inflammation of adipose tissue around nerve roots (8 of 24 rabbits and 7 of 24 dogs) in the brachial plexus sites. The results indicate that EXPAREL was well tolerated in these models and did not produce nerve damage after PNB in rabbits and dogs.