Disposition of human drug preparations in the horse. III. Orally administered alclofenac.

This research study examined how the anti-inflammatory drug alclofenac, administered orally, is distributed and expelled in horses. The study found that detectable concentrations of alclofenac were present in horse plasma for up to 72 hours, and in urine for at least 48 hours post-administration.

Study Methodology and Results

• The researchers administered a dose of 3g of alclofenac to horses orally and then measured the concentrations of the drug in horse plasma and urine through a sensitive high-performance liquid chromatographic process.
• In the plasma, the drug was detectable up to 72 hours post-administration. The plasma disposition, or distribution, of alclofenac in individual horses fit a bi-compartmental model. This model has two successive rate constants, ka1 and ka2, estimated at 0.05 +/- 0.06 h-1 and 0.06 +/- 0.01 h-1 respectively. These constants describe the rate at which the drug is absorbed into and cleared from the body.
• Alclofenac’s half-lives, t1/2 alpha and t1/2 beta, were calculated as 1.0 +/- 0.8 hours and 6.9 +/- 1.5 hours respectively. These results represent the duration of time needed for the amount of the drug in the body to reduce by half in the respective phases. The t1/2 alpha is considered the distribution half-life (the time the drug takes to distribute throughout the body), while t1/2 beta is known as the elimination half-life (the time the body takes to remove half of the drug).
• The peak drug concentration of 38.9 +/- 16.2 micrograms/ml was achieved after around 8.5 +/- 2.4 hours.
• Urine samples showed the presence of alclofenac up to minimum 48 hours after drug administration.
• Within 12 hours, a very small percentage (0.68 +/- 0.19%) of the administered dosage was excreted as unchanged alclofenac, i.e., the drug was largely metabolized. The total alclofenac expelled, including its free and conjugated (metabolized) forms, accounted for 2.16 +/- 0.55% of the administered drug dose.

Implications of the Study

• The study provides important pharmacokinetic data on how orally administered alclofenac is absorbed, distributed, metabolized, and excreted in horses.
• This information is relevant for understanding the drug’s duration of effect, determining appropriate dosage intervals, and predicting potential adverse effects in horses.
• The findings also indicate that a majority of the drug is metabolized by the horse’s body before excretion, contributing further to the understanding of the drug’s pharmacological behavior in this species.