Endotoxin-neutralizing activity of polymyxin B in blood after IV administration in horses.

The research explores the effect of polymyxin B administration, both single and multiple, in horses to treat endotoxemia. The study finds this approach safe and supports repeated intravenous use of the drug as it does not accumulate and is efficiently eliminated from the horses’ system.

Research Methods

• The researchers used five healthy horses to conduct their study, which was split into two parts.
• In the first study, each horse was given an intravenous (IV) dose of polymyxin B and its blood samples collected over 24 hours.
• In the second study, each horse received repeated IV infusions of the antibiotic every eight hours for a total of five treatments. Blood samples were taken until 24 hours after the last dose was administered.
• The scientists measured the concentration of polymyxin B in the horse’s blood by testing its capacity to suppress nitrite production in mouse macrophages stimulated with lipopolysaccharide and interferon-alpha.
• The researchers also collected urine samples from the horses before the first drug infusion and 24 hours after the last one. These were used to determine the ratio of gamma-glutamyl transferase (GGT) to creatinine – two substances that can indicate kidney function.

Research Findings

• The peak serum polymyxin B concentration was detected about 3 micrograms/mL in both studies. Polymyxin B became untraceable 18 hours after the single infusion in the first study.
• In the second study, the maximal polymyxin B concentrations after the first and fifth doses were slightly different, but still hovered around 3 micrograms/mL and 2 micrograms/mL, respectively, indicating that repeated administration didn’t lead to the accumulation of the drug in the horses’ systems.
• The administration of Polymyxin B did not affect the urine GGT-to-creatinine ratios, proving that the drug did not cause any damage to the kidneys of the horses.

Research Conclusion

• The research concludes that polymyxin B given as multiple infusions to healthy horses doesn’t accumulate in the horses’ system and thus, appeared safe to use.
• The results indicate support for the repeated intravenous use of 1 mg of polymyxin B/kg at 8-hour intervals as a treatment for endotoxemia in horses.