Plasma and synovial fluid kinetics, disposition, and urinary excretion of naproxen in horses.

This research explores how the drug Naproxen, used in treating inflammatory conditions in horses, is absorbed, distributed, and excreted after being intravenously given. The findings provide insight into the drug’s kinetics and effects within the horse’s body, including its presence in plasma and synovial fluid, and how it impacts renal excretion.

Study Methodology

• The researchers developed a model to describe Naproxen’s disposition in the body of a horse, including its accumulation and elimination in the synovial fluid after being administered intravenously.
• The drug was administered at a dosage of 5 mg/kg of body weight.

Findings: Plasma Disposition

• Naproxen’s disposition in the plasma was described using a two-compartment model.
• The distribution and elimination half-lives were found to be approximately 1.42 hours and 8.26 hours, respectively.
• The plasma concentration of Naproxen was documented to be 55.3 mg/L at 5 minutes after administration, decreasing to 0.61 mg/L at 48 hours post-administration.
• The steady-state volume of distribution was 0.163 L/kg.
• The area under the plasma concentration time-curve was measured to be 372.1 mg/h/L.

Findings: Synovial Fluid Kinetics

• Peak synovial fluid concentration of the drug was recorded as 12.68 mg/L at 6 hours post-administration, decreasing to 0.71 mg/L at 36 hours.
• The appearance half-life of Naproxen in the synovial fluid was roughly 4.64 hours, and the elimination half-life was about 6.73 hours.

Excretion and Protein Binding

• The total body clearance was measured at 0.015 L/h/kg.
• They found that 97.0% of the drug binds to plasma proteins at plasma concentrations between 5 and 100 mg/L. However, this ratio significantly reduced to 75.2% at plasma concentrations of 0.5, 1, and 500 mg/L.
• The majority of the excreted drug was in the form of glucuronidated Naproxen and unconjugated desmethylnaproxen.

Conclusion

• This study provides valuable insights into how the anti-inflammatory drug Naproxen is absorbed, distributed, and excreted when administered to horses. These findings can help optimize the drug’s use in equine veterinary medicine.