Effect of probenecid on the pharmacokinetics of flunixin meglumine and phenylbutazone in healthy mares.

This research explores the impact of probenecid, a drug often used to treat gout, on the absorption and distribution of flunixin meglumine and phenylbutazone, two anti-inflammatory drugs, in mares. It found that whilst probenecid didn’t significantly change how flunixin meglumine was processed, it did lead to higher concentrations of phenylbutazone in the system.

Overview of the Study

• The investigation was carried out on six healthy mares to gauge the pharmacokinetic properties of flunixin meglumine and phenylbutazone, two anti-inflammatory drugs generally used for treating fevers and mild to moderate pain in horses.
• These drugs were administered intravenously both with and without the concurrent administration of probenecid, a medication typically used to manage gout by preventing the body from reabsorbing uric acid and promoting its expulsion through urine.

Outcomes for Flunixin Meglumine

• The analysis did not show any considerable difference in the pharmacokinetics of flunixin meglumine when administered with or without probenecid.
• This suggests that the concurrent use of probenecid has no notable effect on how flunixin meglumine is processed and utilized in the body of the mares.

Outcomes for Phenylbutazone

• Contrarily, the administration of phenylbutazone with probenecid displayed a significant increase in its 12-hour mean concentration. The level rose from 11.45 micrograms/ml (without probenecid) to 14.56 micrograms/ml (with probenecid).
• This implies that the presence of probenecid can lead to a higher level of phenylbutazone remaining in the mares’ systems compared to when the drug was administered alone.
• Moreover, there was a significant reduction in the volume of distribution at a steady state of the phenylbutazone in conjunction with probenecid. The volume decreased from 218.6 ml/kg (without probenecid) to 169.4 ml/kg (with probenecid).
• The volume of distribution at steady state pertains to how widely and evenly a drug spreads within a body’s tissues and fluids. Thus, this suggests that the probenecid restricts the spread of phenylbutazone in the body.