Metabolism, excretion, pharmacokinetics and tissue residues of phenylbutazone in the horse.

This research article explores the pharmacokinetics, metabolism, excretion, and tissue residues of the drug phenylbutazone (PBZ) in horses. The study found that over a 72-hour period, the drug exists two-phase in the plasma, and its primary metabolites (oxyphenbutazone and gamma-hydroxyphenylbutazone) stay detectable for varying durations. The study also noted that PBZ gets excreted by diffusion in alkaline urine when ingested orally, particularly when food is absent before and after dosing.

Explanation of the Research Paper

• The study specifically investigates phenylbutazone (PBZ), an anti-inflammatory drug commonly administered to horses. The researchers meticulously studied and recorded the drug’s pharmacokinetics, which refers to how a body absorbs, distributes, metabolizes, and excretes a drug.
• The drug was administered to horses both intravenously and orally at a dose rate of 4.4 mg/kg. They used a 72-hour blood sampling schedule and discovered that a third exponential phase was nonexistent; the plasma disposition being represented by a two-compartment open model with particular elimination phase parameters.
• The research then delved into metabolites, which are byproducts of the metabolization process. The drug’s hydroxylated metabolites, oxyphenbutazone (OPBZ) and gamma-hydroxyphenylbutazone (OHPBZ), were found in detectable ranges in plasma for 72 and 24 hours respectively. Another key finding was that, after 36 hours, concentrations of OPBZ exceeded the plasma PBZ concentrations.

Excretion and Tissue Residue Analysis

• In the excretory analysis, the majority of the metabolites found in urine were OPBZ and OHPBZ. However, in lesser concentrations, another compound believed to be gamma-hydroxyoxyphenbutazone (OHOPBZ) was also identified. The researchers collected urine samples at various points in time and found that the percentages of the administered dose recovered from urine were 30.7, 39.0, and 40.3 after 24, 48, and 72 hours respectively.
• The study also found that recovery of PBZ and its metabolites was significantly reduced within the first 24 hours after oral dosing when the horses were permitted unrestricted access to hay. This observation was linked to significantly delayed absorption but was not present in animals deprived of food for a few hours before and after dosing.
• Lastly, the study revealed that PBZ was filtered in minimal amounts due to high plasma protein binding, and then excreted by diffusion trapping in alkaline urine. Significantly higher urine-to-plasma (U/P) concentration ratios were observed for the hydroxylated derivatives, with at least one (OHPBZ) being secreted into urine.