Evaluation of pharmacokinetic and pharmacodynamic properties of cimicoxib in fasted and fed horses.

The article discusses a study that examined how the drug cimicoxib behaves in a horse’s body, and how it affects certain enzymes, based on whether the horse has recently eaten or not. It found that cimicoxib can effectively inhibit these enzymes in both fed and fasted horses.

Study design and methodology

• The study was set up as an open, single dose trial involving two groups of horses – one that had eaten (the fed group) and one that hadn’t eaten for a while (the fasted group). This two-period, crossover design meant each group underwent two phases with a 2-week gap in between.
• Each horse was given an oral dosage of 5mg/kg cimicoxib, a non-steroidal anti-inflammatory drug. The fasted horses were dosed after 12 hours of not eating, and the fed horses were dosed two hours after eating.
• The researchers then collected blood samples from the horses for a period of 24 hours after the drug was administered. This plasma was then used to analyze how the drug behaved in the horses’ bodies, known as pharmacokinetic analysis.

Effect on cyclooxygenase enzymes (COX)

• The team wanted to determine whether cimicoxib inhibits two specific enzymes – cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). These enzymes play a role in inflammation and pain responses in the body.
• So, they measured concentrations of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2), which are indicators of COX-1 and COX-2 activity respectively, in the horse’s blood.

Findings

• After the horses were given cimicoxib, the highest concentration of the drug in the plasma was slightly higher in the fasted horses than in the fed horses. However, it took a longer time to reach this high concentration in the fed group compared to the fasted group. This difference was not statistically significant.
• Both groups of horses showed a significant decrease in the activities of both COX-1 and COX-2 enzymes after receiving the dose of cimicoxib.

Conclusions and further work

• The researchers concluded that while the drug did inhibit both COX-1 and COX-2 enzymes, they did not observe a selective action towards COX-2, which is typically seen with cimicoxib.
• Additionally, they found that cimicoxib could achieve this enzymatic inhibition at a relatively low dosage. However, they concluded that further research is needed to establish a safe and effective dosing regime for clinical use.