Concentrations of dexmedetomidine and effect on biomarkers of cartilage toxicity following intra-articular administration in horses.

This study investigated the post-administration concentrations of dexmedetomidine in horses’ plasma, urine, and synovial fluid. It was shown that this drug persisted longer in synovial fluid than in plasma, and that it effected changes in biomarkers of cartilage health.

Methodology

• The study was conducted on 12 research horses.
• Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline
• Plasma, urine, and synovial fluid samples were collected prior to the administration of the drug, and then over the following 48 hours
• The amounts of dexmedetomidine in these samples were then measured

Markers Of Cartilage Health

• The researchers observed the effects of dexmedetomidine on two biomarkers of cartilage health: CS846, a marker of articular cartilage synthesis, and C2C, a marker of collagen degradation
• The levels of these markers were tested in synovial fluid at 0, 12, and 24 hours after the administration of the drug. They used immunoassays to measure these quantities

Results

• Plasma concentrations of dexmedetomidine fell below the limit of quantification by 2.5 and 8 hours postadministration of 1 and 5 μg/kg respectively
• Synovial fluid concentrations remained above the limit of quantification at 24 hours in both dose groups
• No dexmedetomidine was detected in urine samples taken after the administration of the drug
• In the 5-μg/kg-dose group, CS846 concentrations were significantly increased at 24 hours after the administration of the drug
• In the saline group, CS846 concentrations significantly decreased at 12 hours after the drug was given
• C2C concentrations decreased at 12 and 24 hours after treatment in the saline group. There were no significant differences in CS846 or C2C concentrations between dose groups at any time

Conclusions

• The researchers concluded that dexmedetomidine concentrations remained lower in the system compared to those locally in the synovial fluid
• CS846, a marker which indicates the synthesis of articular cartilage, increased in line with the administered dose
• The results suggest that further study is required to understand the analgesic and adverse effects of this drug, as well as appropriate dosage