Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses.
Abstract: Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a 'no-race day medication' or 24-h rule were carried out. One dosing schedule (oral-i.v.) consisted of 8.8 mg/kg (4 g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2 g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half-bred horses at pasture, and in Thoroughbred horses in training. After administering the i.v. schedule for 4 days to Thoroughbred and Standardbred horses at pasture, the mean plasma concentrations of phenylbutazone increased from 0.77 microgram/ml on day 2 to 2.5 micrograms/ml on day 5. The shape of the frequency distribution of these populations was log-normal. These data are consistent with one horse in 1,000 yielding a plasma level of 8.07 micrograms/ml on day 5. After administration of the oral-i.v. schedule to Thoroughbred and Standardbred horses at pasture, the mean plasma concentrations of phenylbutazone were 3.4 micrograms/ml on day 2 and 3.5 micrograms/ml on day 5. The range on day 5 was from 1.4 to 8.98 micrograms/ml and the frequency distribution was log-normal. These data are consistent with one horse in 1000 having a plasma level of 15.8 micrograms/ml on day 5. In a final experiment, the oral dosing schedule was administered to 62 Thoroughbred horses in training. Plasma concentrations on day 5 in these horses averaged 5.3 micrograms/ml. The range was from 1.3 to 13.6 micrograms/ml and the frequency distribution was log-normal. Statistical projection of these values suggests that following this oral dosing schedule in racing horses about one horse in 1000 will yield a plasma level of 23.5 micrograms/ml of phenylbutazone 24 h after the last dose.
Publication Date: 1984-12-01 PubMed ID: 6512917DOI: 10.1111/j.1365-2885.1984.tb00911.xGoogle Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article involves an experiment conducted to understand the residual concentrations of a drug, phenylbutazone (and its metabolites) in horses that are subject to either oral or intravenous (i.v.) dosing. The study also analyzes the rate at which the drug leaves the body of horses from different breeds and training routines.
Objective and Setup
- The aim was to determine the residual plasma concentrations of the drug and its metabolites in racing horses, under a no-race day medication rule, which prohibits the administration of any drugs within 24-hours from a race.
- Two dosing schedules were set up, one involving oral intake for three days followed by intravenous dosing on the fourth day, and another where intravenous dosing was provided for four consecutive days.
- The study encompassed horses from two different breeds, Thoroughbred and Standardbred, both in natural pasture environments and training conditions.
Findings
- After the four-day intravenous dosing schedule, the average concentrations of phenylbutazone increased significantly in horses.
- The distribution of drug residues followed a log-normal pattern which means most individuals in a population are close to the average rate of elimination with few outliers.
- The study indicates an oral–intravenous dosing regimen resulted in slightly higher concentrations, also distributed in a log-normal pattern.
- Following the oral dosing schedule, the horses in training had higher concentrations on average, and the range of concentrations was also notably higher than in the pasture-fed horses.
- Statisticians found that one in 1,000 horses may present a post-race plasma level significantly higher than the observed mean.
Implications
- The results, while preliminary, suggest that the dosing schedule, method and the natural setting of the horse can affect the residual plasma concentrations of phenylbutazone.
- This has extensive implications for racing horses’ management, particularly where drugs are commonly used for performance or recovery.
- Furthermore, the findings indicate that depending on the horse’s specific dosing schedule and other factors, there may be instances where drug residues remain in notable concentrations, even 24-hours after administration.
Cite This Article
APA
Chay S, Woods WE, Nugent TE, Weckman T, Houston T, Sprinkle F, Blake JW, Tobin T, Soma LR, Yocum J.
(1984).
Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses.
J Vet Pharmacol Ther, 7(4), 265-276.
https://doi.org/10.1111/j.1365-2885.1984.tb00911.x Publication
Researcher Affiliations
MeSH Terms
- Administration, Oral
- Animals
- Drug Administration Schedule
- Female
- Horses / metabolism
- Injections, Intravenous
- Kinetics
- Male
- Oxyphenbutazone / blood
- Phenylbutazone / blood
- Physical Conditioning, Animal
- Therapeutic Equivalency
Citations
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