Effect of probenecid administration on cephapirin pharmacokinetics and concentrations in mares.

This research investigates the impact of using Probenecid on the pharmacokinetics and concentrations of Cephapirin in mares. The results suggest that administering Probenecid alongside Cephapirin significantly increases the concentration of Cephapirin in serum, peritoneal fluid, synovial fluid, and the endometrium.

Research Methodology

• The researchers used a controlled experiment design on two mares, where Cephapirin was administered intravenously, both before and after 3 doses of Probenecid (administered intragastrically).
• Different doses of Probenecid (25, 50, or 75 mg/kg) were administered at twelve-hour intervals.
• The researchers calculated clearance and apparent volume of distribution based on the observed areas under the curve, to understand how Probenecid dose affects these aspects.

Main Findings

• The findings showed that there was a negative correlation between Probenecid dose and both clearance and apparent volume of distribution of Cephapirin.
• Also, the research found that administration of 50 mg of Probenecid/kg reduced Cephapirin clearance by approximately 50%.
• Furthermore, concentrations of Cephapirin in serum, synovial fluid, peritoneal fluid, cerebral spinal fluid, urinary, and endometrial areas were observed after administering 5 doses of Cephapirin – both separately and alongside Probenecid.
• The highest mean serum Cephapirin concentrations were observed half an hour after the fifth Cephapirin dose (16.1 +/- 2.16 micrograms/ml) in mares not given Probenecid and 1.5 hours after the fifth Cephapirin dose (23.7 +/- 1.30 micrograms/ml) in mares given Probenecid.
• Notably, mean peak peritoneal fluid and synovial fluid Cephapirin concentrations were higher when Probenecid was administered alongside.

Conclusion

• The study concluded that the administration of Probenecid concurrently with Cephapirin led to statistically higher concentrations of Cephapirin in the serum, peritoneal fluid, synovial fluid, and the endometrium, ultimately influencing the pharmacokinetics of Cephapirin in mares.