Plasma and synovial fluid concentrations and cartilage toxicity of bupivacaine following intra‐articular administration of a liposomal formulation to horses

Abstract

Sustained concentrations of IA bupivacaine suggest viability of this medication as an intra-articular analgesic. Effects on equine chondrocytes need further study.

Effect of bupivacaine concentration and formulation on canine chondrocyte viability in vitro

“…The half‐life of liposomal bupivacaine in canine joints is unknown. Previous researchers evaluating the half‐life in equine joints found a half‐life of 16.4 ± 5.4 hours within synovial fluid, which was similar to the plasma half‐life 18 ; this is much shorter than the plasma half‐life of 36.2 ± 12.4 hours after subcutaneous injection reported in dogs 24 . This provides evidence that there is more rapid elimination of LEB from the joint space than from the subcutaneous space, although it may remain present for longer than in the treatment times used in this and previous studies 16 …”

“…There was a difference between the 0.6 mg/mL and the 2.5 mg/mL SFB groups ( # P = .03). 50:50 LEB, 50% dilution of LEB in saline; CCGM, canine chondrocyte growth medium; LEB, liposomal encapsulated bupivacaine; SFB, standard formulation bupivacaine in equine joints found a half-life of 16.4 ± 5.4 hours within synovial fluid, which was similar to the plasma half-life 18 ; this is much shorter than the plasma half-life of 36.2 ± 12.4 hours after subcutaneous injection reported in dogs. 24 This provides evidence that there is more rapid elimination of LEB from the joint space than from the subcutaneous space, although it may remain present for longer than in the treatment times used in this and previous studies.…”

“…Recently, a liposomal‐encapsulated formulation of bupivacaine (LEB) has become available for veterinary use. Preclinical studies in cows, horses, and pigs have failed to provide evidence that this formulation results in a significant chondrotoxic effect compared with standard formulations of bupivacaine (SFB) 16‐18 . To the best of the authors' knowledge, no research has been conducted to evaluate the effect of LEB on canine chondrocytes.…”

Evaluation of Intra-Articular Amikacin Administration in an Equine Non-inflammatory Joint Model to Identify Effective Bactericidal Concentrations While Minimizing Cytotoxicity

“…Limitations to the study design include the small horse sample size, evaluation in normal vs. inflamed joints, lack of synovial fluid collection at later time points for biomarker analysis to investigate when inflammatory cytokine concentrations returned to baseline, and the lack of histopathologic evaluation of synovial tissues. Obtaining a bigger sample size and performing additional sampling of the synovial fluid past 24 h were not possible due to financial constraints, but may have revealed continued increases in the biomarkers of collagen degradation and potentially statistically significant elevations in the CRP values, as has been previously reported (34). Furthermore, synovial fluid sampling at later time points and evaluation of the histopathology of synovial tissues may have provided further information as to whether intra-articular amikacin administration resulted in long-term joint damage or was only associated with a transient increase in pro-inflammatory cytokines and cartilage degradation products.…”

“…Competitive ELISAs, previously validated for equine samples (IBEX Pharma, Quebec, Canada), were used to measure the concentrations of biomarkers C2C (biomarker of type II collagen degradation) and C12C [biomarker of type I (soft tissue) and type II (cartilage) collagen degradation] in the SF from all treatment groups collected at time points 0, 8, and 24 h as previously described (34).…”