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

The research examines the concentration and potential cartilage toxicity of the local anesthetic bupivacaine, delivered by intra-articular administration in a liposomal formulation, on horses. The study also measures biomarkers as an indication of the drug’s effects on cartilage cells.

Objectives and Methodology of the Research

The main objective of the study was to:

• Describe bupivacaine’s concentrations when administered intra-articularly, and
• Evaluate biomarkers as indicators of the effects liposomal bupivacaine has on chondrocytes, or cartilage cells, in the horse’s body.

To conduct this study, a total of sixteen horses, which were undergoing exercise, were selected. One group of horses received a single intra-articular dose of 0.12 mg/kg of liposomal bupivacaine, while another group received 0.9% saline. The team collected blood and urine samples for a period spanning 96 hours post-drug administration.

Measurement, Analysis and Results

The drug concentrations were measured using a method called LC-MS/MS (liquid chromatography-mass spectrometry) and were analyzed through pharmacokinetic analysis.

Animal-specific biomarkers related to collagen degradation (C2C, C12C) and cartilage matrix synthesis (CPII, CS846) were measured in the synovial fluid using a method called immunoassays.

The results indicated that the half-life of bupivacaine in horse plasma was 17.8 ± 5.42 hours and 11.9 ± 5.17 hours for the groups of horses from which synovial fluid was collected daily and 96 hours respectively. Furthermore, bupivacaine concentrations in the joint were still detectable at 96 hours post-administration.

Significant increases in C12C and C2C were observed at the 96-hour mark in horses that underwent arthrocentesis only at the end of the 96 hours. In this context, arthrocentesis refers to the clinical procedure of using a syringe to collect synovial fluid from a joint capsule. The CPII marker increased at 48 hours, and the CS846 marker showed increase at 24 and 48 hours in horses that were sampled daily.

Conclusion and Limitations

The study concluded that sustained concentrations of intra-articular bupivacaine suggest its potential as a long-term analgesic for joint pain in horses. However, the exact effects of the drug on equine chondrocytes require further investigation.

The research also acknowledged the limitations of the study, including the limited number of sampled animals and the absence of a liposome control group, which could affect the validity and generalizability of the results.