Pharmacodynamics and pharmacokinetics of carprofen in the horse.

The study investigates how the drug carprofen, used for treating inflammation, is metabolised and functions in horses. The research shows that while the drug does reduce swelling at the site of inflammation, it does not decrease the number of white blood cells in the inflammation fluid.

Pharmacokinetics and Pharmacodynamics of Carprofen

• The research was conducted using a model of non-immune inflammation in six horses. In this setup, the team administered 0.7 mg of carprofen per kg of the horse’s body weight intravenously.
• The main focus of the study was to isolate and understand pharmacokinetic parameters such as elimination half-life, volume of distribution, clearance rate, and the area under the plasma concentration time curve, all of which were collected and analysed post administration of the drug.

Resulting Carprofen Concentration and Levels of Inflammation

• The team measured the ratio of the carprofen concentration in the inflammation exudate (fluid) to the plasma and found that it was greater than 1 at all sampling times between 2 and 48 hours. This indicates that the drug was present at higher concentrations in the inflamed tissues.
• When it came to the drug’s pharmacodynamics, it was found that carprofen significantly reduced swelling at the site of inflammation. However, the number of white blood cells in the inflammation exudate remained unaffected.

Carprofen’s Mechanism of Action

• The study also found that carprofen moderately suppressed the synthesis of two key inflammation mediators – serum thromboxane B2 and exudate prostaglandin E2. Interestingly, these effects were not directly related to the concentration of carprofen in the plasma or the exudate.
• From this observation, the researchers concluded that the anti-swelling (anti-oedematous) effect of carprofen was not due to an inhibition of the cyclo-oxygenase enzyme. This enzyme is usually responsible for the production of prostaglandins and thromboxanes, substances that often cause inflammation and pain. This finding was unexpected and suggests that carprofen operates through different mechanisms to reduce inflammation.