Pharmacokinetics and in vitro efficacy of salicylic acid after oral administration of acetylsalicylic acid in horses.

The research explores the concentrations of Salicylic acid (SA), a metabolite of Acetylsalicylic acid (ASA), produced in horses’ plasma and urine after administering three varying dosages of ASA. The study finds that the current thresholds established for SA levels may be too high, potentially allowing ASA’s misuse in horses.

Research Objectives and Methodology

• This research was undertaken to study the progress stages of Salicylic acid (SA), a metabolite of Acetylsalicylic acid (ASA), in horses’ plasma and urine after the oral intake of ASA. The understanding of SA’s metabolization rate can justify the thresholds established by horse sport organizations.
• The experiment was cross-designed; eight horses were administered ASA at three single dosages – 12.5 mg/kg, 25 mg/kg, and 50 mg/kg.
• After administration, both plasma and urine samples were examined periodically for SA concentration.

Key Findings

• SA concentration peaks varied across the dosage groups. The 12.5 mg/kg and 25 mg/kg groups saw peak concentrations in urine 2 hours post-ASA administration. The peak plasma concentrations across these groups were observed 1.5 hour post-dosage.
• The 50 mg/kg group presented a delayed response, with peak urine and plasma SA concentrations observed after 5 and 1.5 hours respectively.
• The plasma half-life for SA ranged between 5.0 and 5.7 hours, suggesting that half the administered ASA took around 5 hours to be metabolised into SA.
• Urine concentration of SA fell below the set threshold of 750 μg/mL between 7-26 hours after administering 12.5 and 25mg/kg ASA and between 24-36 hours after administering 50 mg/kg ASA.
• It could not be possible to calculate an inhibition concentration (IC) for SA, due to insufficient inhibition of cyclooxygenases, indicating SA’s low efficacy in inhibiting these enzymes.

Conclusion

• The study’s findings indicate that the present thresholds of SA levels, set at 750 μg/mL urine and 6.5 μg/mL plasma, may actually be too high – thus posing a risk of ASA misuse in horses.
• This might happen since the metabolized amount of SA (from ASA) could be manipulated to remain under the threshold for longer periods, making it harder for investigators to detect the drug misuse.