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

Brigitte M Richard, Paul Newton, Laura R Ott, Dean Haan, Abram N Brubaker, Phaedra I Cole, Paul E Ross, Marlon C Rebelatto, Keith G Nelson, Brigitte M Richard, Paul Newton, Laura R Ott, Dean Haan, Abram N Brubaker, Phaedra I Cole, Paul E Ross, Marlon C Rebelatto, Keith G Nelson

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.

Figures

Figure 1
Figure 1
Injection site findings (Day 3) in a female rabbit (a) or dog (b) of the EXPAREL 18 mg/kg (a) and 25 mg/kg (b) showing granulomatous inflammation of adipose tissue. H&E 20X.
Figure 2
Figure 2
Mean pharmacokinetic profile of EXPAREL in rabbits from 0–24 hours (a) and 0–96 hours (b).
Figure 3
Figure 3
Mean pharmacokinetic profile of EXPAREL in dogs from 0–24 hours (a) and 0–96 hours (b).

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Source: PubMed

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