Pharmacokinetics of phenylbutazone and its metabolites in the horse.

Abstract

Phenylbutazone was given orally to 2 groups of horses and the plasma levels of the drug and its 2 principal metabolites oxyphenbutazone and gamma-hydroxyphenylbutazone measured by high performance liquid chromatography. Animals in Group 1 received single oral doses in a range from 1.1 to 13.2 mg/kg and were sampled over the succeeding 24 h. Considerable individual variation was observed both in timing and magnitude of the plasma drug responses between horses, but 24 h after dosing a clear dose response relation was recorded. Group 2 horses were given the recommended therapeutic dosage regimen and sampled over 24 h periods twice weekly. After 4 days at 8.8 mg/kg in 2 divided doses mean peak plasma levels of phenylbutazone reached 24 micrograms/ml and showed evidence of cumulation. After 4 days at 4.4 micrograms/kg, peak plasma concentrations had fallen to 10 micrograms/ml and mean peak levels just failed to reach 4 micrograms/ml 3 days after reducing dosage to 2.2 mg/kg once daily. Plasma concentrations of oxyphenbutazone did not exceed 25 per cent of the parent drug and the gamma-hydroxy metabolite was only just detectable and never exceeded 1 microgram/ml.