Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses.

This study explored the pharmacokinetics of an anti-inflammatory drug called Phenylbutazone (PBZ) used on horses, administered both orally and intravenously. The study focused on examining the concentrations of this drug in the blood and urine of the horse subjects, as well as assessing the duration and effects of the drug on indicators of inflammation.

Research Methodology

A total of 35 horses participated in this study. Intravenous administration of PBZ was given to 17 of these horses, while the remaining 18 received it orally, with both groups receiving a dose of 2g. Researchers collected samples of the horses’ blood and urine prior to and up to 96 hours after administering the PBZ.

• For an ex vivo synthesis of eicosanoids, blood samples were taken at various intervals and challenged with substances known as lipopolysaccharide or calcium ionophore.
• The concentration levels of PBZ and eicosanoids were then measured using a method called “liquid chromatography-tandem mass spectrometry” (LC-MS/MS).
• A non-compartmental pharmacokinetic analysis was applied to the concentration data gathered from the intravenous and oral administration.

Key Findings

Results indicated that serum levels of PBZ and its byproducts were below the limit of quantification 96 hours after administering the drug. Specific pharmacokinetic parameters such as the volume of distribution at steady state, systemic clearance, and terminal half-life following both intravenous and oral administration were also measured.

• The rates of these parameters were computed as 0.194 ± 0.019 L/kg, 23.9 ± 4.48 mL/h/kg, and 10.9 ± 5.32 hours respectively.
• The terminal half-life after oral administration was 13.4 ± 3.01 (paste) and 15.1 ± 3.96 hours (tablets).
• The blood, treated with PBZ and subjected to a stimulus of lipopolysaccharide and calcium ionophore, demonstrated an inhibition of TXB, PGE, LTB, and 15-HETE production for a long period after drug administration. These compounds signify inflammation, thus their reduction indicates a decrease in inflammation triggered by PBZ.

According to the findings from this research, it appears that PBZ has a prolonged anti-inflammatory effect in horses after being administered either orally or intravenously at a dosage of 2g.