Pharmacokinetics of phenylbutazone and its metabolites in the horse.

This study explores the pharmacokinetics of phenylbutazone and its metabolites in horses, observing how the body metabolizes, distributes and eliminates the drug. Findings show considerable variation among horses and an apparent dose-response relationship.

Research Design

• Two groups of horses were administered oral doses of phenylbutazone, after which the plasma levels of the drug and its primary metabolites were measured.
• High performance liquid chromatography was used to measure the drug levels.

Results

• The research saw significant individual variation in timing and magnitude of plasma drug responses between horses.
• With the passage of 24 hours after dosing, a clear dose-response relationship was established.

Group Comparisons

• The horses in Group 1 received single oral doses ranging from 1.1 to 13.2 mg/kg and were sampled over the following 24 hours.
• Horses in Group 2 took the recommended therapeutic dosage and were sampled every 24 hours twice weekly.
• In Group 2, after 4 days at 8.8 mg/kg in two separate doses, mean peak plasma levels of phenylbutazone reached 24 micrograms/ml, which indicated evidence of cumulation.
• After another 4 days of this dosage, the peak plasma concentrations fell to 10 micrograms/ml, and mean peak levels dropped to less than 4 micrograms/ml three days after the dosage was reduced to 2.2 mg/kg once daily.

Measured Metabolites

• The plasma concentrations of oxyphenbutazone, the metabolite of phenylbutazone, never exceeded 25% of the parent drug.
• The gamma-hydroxy metabolite was scarcely detectable and never exceeded 1 microgram/ml.

This research demonstrated the varying impacts of drug dosage on its concentration levels in horse plasma, as well as the conversion of the drug into its metabolites. In application, it offers useful insights to pharmacologists and medical professionals on the side effects of varying dosages of phenylbutazone on horses.