Protein binding and in vitro serum thromboxane B2 inhibition by flunixin meglumine and meclofenamic acid in dog, goat and horse blood.

The study investigates the effects of the drugs flunixin meglumine and meclofenamic acid on protein binding and inhibition of thromboxane B2, a biological compound associated with inflammation and blood clotting, in the blood serum of dogs, goats, and horses. It found that both drugs were strongly bound to proteins in serum and inhibited thromboxane B2 production effectively.

Protein Binding of Flunixin and Meclofenamic Acid

• The research demonstrates substantial protein binding of flunixin in the blood serum of dogs (92.2%), goats (84.8%), and horses (86.9%).
• Meclofenamic acid was also found to be highly protein bound, with varying percentages among the different animal species – 90.3% in dogs, 84.7% in goats, and 99.8% in horses.

Inhibition of Thromboxane B2 Generation

• Both flunixin and meclofenamic acid acted as potent inhibitors of the in vitro (in a controlled laboratory setting) generation of thromboxane B2 in blood.
• The concentration of flunixin needed to inhibit 50% of thromboxane B2 (IC50) production was 0.10 µM for dogs, 0.02 µM for goats, and 0.04 µM for horses. The concentration required to inhibit 100% (Imax) was 2.07 µM for both dogs and horses and 0.14 µM for goats.
• For meclofenamic acid, the IC50 values were 0.77 µM for dogs, 0.80 µM for goats, and 0.30 µM for horses. The Imax values were 3.93 µM for dogs, 3.63 µM for goats, and 3.56 µM for horses.

Protein Binding Corrected Concentrations

• The study also calculated the amount of drug required for thromboxane B2 inhibition after accounting for protein binding. For flunixin, these corrected IC50 values were 0.008 µM for dogs, 0.003 µM for goats, and 0.005 µM for horses.
• The corrected IC50 values for meclofenamic acid were found to be 0.075 µM for dogs, 0.122 µM for goats, and 0.001 µM for horses.

In conclusion, both flunixin and meclofenamic acid exhibit significant protein binding abilities and could inhibit thromboxane B2 production in the blood of dogs, goats, and horses. This research might aid in developing/optimizing drug dosages to control inflammation and blood clotting in veterinary medicine.