Phenylbutazone and its metabolites in plasma and urine of thoroughbred horses: population distributions and effects of urinary pH.

Abstract: A survey of plasma and urinary concentrations of phenylbutazone and its metabolites in thoroughbred horses racing in Kentucky was carried out. Post-race blood samples from more than 200 horses running at Latonia Racetrack and Keeneland in the Spring of 1983 were analysed. The modal plasma concentration of phenylbutazone was between 1 and 2 micrograms/ml, the mean concentration was 3.5 micrograms/ml and the range was up to 15 micrograms/ml. Oxyphenbutazone had a modal plasma concentration between 1 and 2 micrograms/ml, a mean concentration of 2.07 micrograms/ml and a range of up to 13 micrograms/ml. gamma OH-phenylbutazone had a modal plasma concentration of less than 1 microgram/ml, a mean level of 1.39 micrograms/ml and a range of up to 7.32 micrograms/ml. All plasma concentration frequency distributions were well fitted by log normal distributions. Urinary concentrations of phenylbutazone yielded modal concentrations of less than 1 microgram/ml, a mean urinary concentration of 2.9 micrograms/ml, with a range of up to 30.5 micrograms/ml. This population fitted a log-normal distribution. For oxyphenbutazone the modal concentration was less than 3 micrograms/ml, the mean concentration was 15.26 micrograms/ml, with a range to 81.5 micrograms/ml. The frequency distribution of these samples was apparently bimodal. For gamma OH-phenylbutazone, the modal concentration was less than 4 micrograms/ml, the mean concentration 21.23 micrograms/ml, with a range of up to 122 micrograms/ml. The population frequency distribution for gamma OH-phenylbutazone was indeterminate. Analysis of the pH of these post-race urine samples showed a bimodal frequency distribution. The pH values observed ranged from 4.9 to 8.7, with peaks at about pH 5.25 and 7.25. This bimodal pattern of urinary pH values is consistent with observations made in England and Japan. Urinary pH influenced the concentrations of phenylbutazone, oxyphenbutazone and gamma OH-phenylbutazone found in the urine samples. The concentration of these metabolites found in alkaline urines were from 32 to 225 times greater than those found in acidic urines. Plasma concentrations of phenylbutazone and its metabolites, however, were unaffected by urinary pH. In interlaboratory experiments, horses running at Hollywood Park were dosed with phenylbutazone at about 2 g/1000 lbs 24 and 48 h before racing, and a mean dose of 0.6 g/1000 lbs at 72 h prior to racing. Post-race plasma samples from these horses showed phenylbutazone concentrations ranging from 0.44 to 9.97 micrograms/ml, with a mean concentration of 4.09 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)