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

BACKGROUND: The use of intra‐articular (IA) local anaesthetics has proven to be an effective means to treat post‐operative pain. The effects of local anaesthetics on equine chondrocytes are mixed with some studies reporting chondrodestruction and others no adverse effects. A liposomal formulation of bupivacaine is used in people and dogs by intra‐ and peri‐articular administration to provide up to 72 h of analgesia. The potential uses, side effects including chondrotoxicity, and likelihood of abuse (long‐term analgesic effects) has not been evaluated in horses. OBJECTIVES: Describe bupivacaine concentrations following IA administration and assess biomarkers as indicators of the effects of liposomal bupivacaine on chondrocytes in vivo. STUDY DESIGN: Parallel design. METHODS: Sixteen exercised horses received a single IA administration of 0.12 mg/kg liposomal bupivacaine or 0.9% saline. Blood and urine samples were collected for 96 h post‐drug administration. Six horses treated with bupivacaine and those receiving saline, underwent daily arthrocentesis. Six additional bupivacaine treated horses underwent arthrocentesis at 96 h. Drug concentrations were measured using LC‐MS/MS and pharmacokinetic analyses performed. Immunoassays were used to measure markers of collagen degradation (C2C, C12C) and cartilage matrix synthesis (CPII, CS846) in synovial fluid. RESULTS: The bupivacaine plasma elimination half‐life was 17.8 ± 5.42 and 11.9 ± 5.17 h for horses from which synovial fluid was collected daily and at 96 h respectively. Bupivacaine concentrations in the joint were still detectable at 96 h. Significant increases in C12C and C2C were noted at 96 h in horses undergoing arthrocentesis at 96 h only. CPII was increased at 48 h and CS846 at 24 and 48 h in horses sampled daily. MAIN LIMITATIONS: Limited number of animals and absence of liposome control group. CONCLUSIONS: Sustained concentrations of IA bupivacaine suggest viability of this medication as an intra‐articular analgesic. Effects on equine chondrocytes need further study.