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

Abstract

Houston, T., Chay, S., Woods, W.E., Combs, G., Kamerling, S., Blake, J.W., Edmundson, A.G., Vessiney, R. & Tobin, T. Phenylbutazone and its metabolites in plasma and urine of thoroughbred horses: population distributions and effects of urinary pH. J. vet. Pharmacol. Therap. 8, 136–149. A survey of plasma and urinary concentrations of phenylbutazone and its metabolites in thoroughbred horses racing in Kentucky was carried out. Poat-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 2µg/ml, the mean concentration was 3.5µg/ml and the range was up to 15µg/ml. Oxyphenbuta-zone had a modal plasma concentration between 1 and 2µg/ml, a mean concentration of 2.07µg/ml and a range of up to 13µg/ml. _γOH-phenylbutazone had a modal plasma concentration of less than 1µg/ml, a mean level of 1.39µg/ml and a range of up to 7.32µg/ml. All plasma concentration frequency distributions were well fitted by log normal distributions. Urinary concentrations of phenylbutazone yielded modal concentrations of less than 1µg/ml, a mean urinary concentration of 2.9µg/ml, with a range of up to 30.5µg/ml. This population fitted a log-normal distribution. For oxyphen-butazone, the modal concentration was less than 3µg/ml, the mean concentration was 15.26µg/ml, with a range to 81.5µg/ml. The frequency distribution of these samples was apparently bimodal. For _γOH-phenylbutazone, the modal concentration was less than 4µg/ml, the mean concentration 21.23µg/ml, with a range of up to 122µg/ml. The population frequency distribution for _γOH-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, oxyphenbuta-zone and _γOH-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 2g/1000 lbs 24 and 48 h before racing, and a mean dose of 0.6g/1000 lbs at 72 h prior to racing. Post-race plasma samples from these horses showed phenylbutazone concentrations ranging from 0.44 to 9.97µg/ml, with a mean concentration of 4.09µg/ml. Plasma oxyphenbutazone concentrations in these horses varied from 0.8µg/ml to 11.3µg/ml, with a mean of 5.3µg/ml. Comparison of plasma concentrations of phenylbutazone and oxyphenbutazone in horses racing in Kentucky, with the results of dosing experiments in horses in training, suggests that most horses racing in Kentucky are being dosed with amounts of phenylbutazone broadly equivalent to, or less than, proposed ‘no-race-day medication rule’ dosing schedules. T. Tobin, Kentucky Equine Drug Research and Testing Programs, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0076, U.S.A.