title: The Safety of EXPAREL ® (Bupivacaine Liposome Injectable Suspension) Administered by Peripheral Nerve Block in Rabbits and Dogs.
abstract: 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 C(max) 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.
authors.affiliation: Clinical Research and Drug Safety Assessment, Pacira Pharmaceuticals, Inc., 10450 Science Center Drive, San Diego, CA 92121, USA.
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Richard
authors.forename: Paul
authors.initials: P
authors.lastname: Newton
authors.forename: Laura R
authors.initials: LR
authors.lastname: Ott
authors.forename: Dean
authors.initials: D
authors.lastname: Haan
authors.forename: Abram N
authors.initials: AN
authors.lastname: Brubaker
authors.forename: Phaedra I
authors.initials: PI
authors.lastname: Cole
authors.forename: Paul E
authors.initials: PE
authors.lastname: Ross
authors.forename: Marlon C
authors.initials: MC
authors.lastname: Rebelatto
authors.forename: Keith G
authors.initials: KG
authors.lastname: Nelson