Enantiospecific pharmacokinetics of ketoprofen in plasma and synovial fluid of horses with acute synovitis.

The research article presents details of a study on the pharmacokinetics of ketoprofen, a nonsteroidal anti-inflammatory drug, given to horses with acute synovitis, in particular, examining the different effects of the two enantiomers of the drug.

Study Design

• The study was designed as a four-period cross-over study, which means that the same group of horses were treated in different ways at different times, allowing for a comparison of effects while controlling for individual differences among the horses. In this case, the horses were six in number; five mares and one gelding.
• The horses in the study were administered the drug ketoprofen (KTP) in three different ways. They were either given a mixture of both enantiomers of the drug (also known as a racemic mixture) at a dose of 2.2 mg/kg, or they were given one or the other enantiomer individually at a dose of 1.1 mg/kg. The enantiomers are simply two forms of the same molecule that are mirror images of each other. They can sometimes have differing effects in the body.

Results and Findings

• Following administration, the researchers found that the S(+) enantiomer of ketoprofen was the predominant form in both the blood plasma and the synovial fluid of the horses, regardless of whether the racemic mixture or the enantiomers were given.
• The researchers observed that there was unidirectional inversion of the R(-) ketoprofen to the S(+) form, but this inversion was lesser than what previous reports have suggested.
• The team also noted that the presence of an inflammatory reaction could cause this reduction due to its impact on liver metabolism.
• The study also showed that the concentrations of both S(+) and R(-) ketoprofen in synovial fluid were low and short-lasting which was not expected.
• Even after administration of the R(-) ketoprofen, significant portions of the S(+) form was detected in the synovial fluid, suggesting some conversion of the drug forms in the body.

Implications

• These findings help increase the understanding of how ketoprofen, a commonly used anti-inflammatory drug, behaves in the body. This is crucial in dosing and predicting its efficacy in treating conditions.
• It also raises questions on the inversion process and efficiency of ketoprofen and its impact in medical and pharmacological applications.
• Additionally, the results suggest the need to consider the status of inflammation when prescribing doses of drugs, as it may affect the drug’s metabolism in the body.