Pharmacokinetics and synovial fluid concentrations of flurbiprofen enantiomers in horses: chiral inversion.

This research paper studies the pharmacokinetics and synovial fluid concentrations of enantiomers of Flurbirpofen (a non-steroidal anti-inflammatory drug) in horses. The study found no chiral inversion and no stereoselective differences, suggesting a different pharmacokinetic behavior compared to other similar acids.

Introduction to Flurbirpofen and its Enantiomers

• Flurbirpofen (FBP) is a popular nonsteroidal anti-inflammatory drug (NSAID), known for its analgesic and anti-inflammatory properties. It belongs to the 2-aryl propionate class.
• In commercial form, Flurbirpofen is a racemic mixture, containing equal amounts of the R(-) and S(+) enantiomers. These are simply two forms of the FBP molecule that are mirror images of each other.

Details of the Study:

• The research aimed at investigating the metabolic chiral inversion of FBP. This is a phenomenon where one enantiomer converts into its mirror image after administration.
• In this experiment, each enantiomer was administered separately, and then together in a racemic mixture, into horses intravenously.
• The plasma and synovial fluid concentrations of each enantiomer was then measured, and their dispositional behaviour analysed.

Key Findings

• A significant result of the study was that no chiral inversion was detected in horses, either after individual or racemic administration of FBP.
• The pharmacokinetic parameters of the two enantiomers were also found to be identical. These Parameters include clearance rate, volume of distribution, mean residence time, and area under the curve (AUC) for plasma drug concentration versus time.
• In addition, the concentration of Flurbirpofen in synovial fluid was uniformly lower than plasma concentrations, which suggests that both enantiomers penetrate synovial fluid in a similar fashion.

Conclusion

• This study concluded that the disposition of FBP in horses is not enantioselective, indicating that the body doesn’t preferentially metabolize or eliminate one enantiomer over the other.
• Finally, the researchers noted that FBP enantiomers behave differently compared to the enantiomers of other 2-aryl-propionic acids like carprofen, ketoprofen and vedaprofen in horses. This highlights a possibility of different mechanism of action or metabolic pathway for FBP in horses.