The effect of inflammation on the disposition of phenylbutazone in thoroughbred horses.
Abstract: The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study (n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg (n = 5) or 4.4 mg/kg (n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. Inflammation did not appear to affect the plasma kinetics or the urinary excretion of PBZ and its metabolites, oxyphenbutazone (OPBZ) or hydroxyphenylbutazone (OHPBZ) when PBZ was administered at 8.8 mg/kg. However, small but significant increases (P < 0.05) in total body clearance (CLB; 29.2 +/- 3.9 vs. 43.8 +/- 8.1 mL/ h.kg) and the volume of distribution, calculated by area (Vd(area); 0.18+/- 0.05 vs. 0.25 +/- 0.03 L/kg) or at steady-state (Vd(SS); 0.17 +/- 0.04 vs. 0.25 +/- 0.03 L/ kg), were obtained in horses after adjuvant injection, compared to controls, when PBZ was administered at 4.4 mg/kg which corresponded to relatively higher tissues concentrations and lower plasma concentrations (calculated) at the time of maximum peripheral PBZ concentration. Soft tissue inflammation also induced a significantly (P < 0.05) higher amount of OPBZ in the urine 18 h after PBZ administration but the total urinary excretion of analytes over 48 h was unchanged. These results have possible implications regarding the administration of PBZ to the horse close to race-day.
Publication Date: 1996-12-01 PubMed ID: 8971677DOI: 10.1111/j.1365-2885.1996.tb00085.xGoogle Scholar: Lookup
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- Journal Article
Summary
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The research investigates how inflammation affects the way Thoroughbred horses’ bodies process a drug called phenylbutazone. Results suggest that inflammation has minimal effect on the drug’s behavior in the body for standard doses and the influence only becomes significant with higher drug concentrations.
Study Design
- The study was performed on Thoroughbred horses, with a preliminary section done using 5 horses to ascertain whether injection of phenylbutazone (PBZ) would impact the plasma kinetics of further doses.
- The same five horses, along with four new additions, were given PBZ—either an 8.8 mg/kg dosage or a 4.4 mg/kg dosage.
- After giving the drug, soft tissue inflammation was artificially induced using Freud’s adjuvant, an inflammatory agent.
- The drug administration was repeated five weeks later using an equivalent dose as was given before the inflammation was induced.
Results
- The inflammation did not seem to significantly influence the plasma kinetics or the urinary excretion of PBZ and its metabolites when the drug was given at an 8.8 mg/kg dosage.
- However, when given at a 4.4mg/kg dosage, there were small but statistically significant increases observed in total body clearance and volume of distribution after inducing inflammation.
- It was found that the drug, when given at a 4.4 mg/kg dose, corresponded to relatively higher tissue concentrations and lower plasma concentrations at the time of maximum peripheral PBZ concentration after inducing inflammation.
- 18 hours after PBZ administration, there was a significantly larger amount of a PBZ metabolite called oxyphenbutazone (OPBZ) found in the horse’s urine following inflammation induction. Despite this, the total urinary excretion of analytes over 48 hours remained unchanged.
Implications
- This study may have implications for the administration of PBZ to horses near race days, as the presence and degree of inflammation might impact the rate of PBZ clearance from the body.
Cite This Article
APA
Mills PC, Ng JC, Auer DE.
(1996).
The effect of inflammation on the disposition of phenylbutazone in thoroughbred horses.
J Vet Pharmacol Ther, 19(6), 475-481.
https://doi.org/10.1111/j.1365-2885.1996.tb00085.x Publication
Researcher Affiliations
- Department of Veterinary Pathology, University of Queensland, Australia.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- Anti-Inflammatory Agents, Non-Steroidal / blood
- Anti-Inflammatory Agents, Non-Steroidal / metabolism
- Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
- Anti-Inflammatory Agents, Non-Steroidal / urine
- Biological Availability
- Blood Specimen Collection
- Chromatography, High Pressure Liquid / veterinary
- Dose-Response Relationship, Drug
- Freund's Adjuvant / administration & dosage
- Freund's Adjuvant / toxicity
- Half-Life
- Horses
- Inflammation / chemically induced
- Inflammation / physiopathology
- Injections, Intravenous / veterinary
- Male
- Oxyphenbutazone / blood
- Oxyphenbutazone / urine
- Phenylbutazone / administration & dosage
- Phenylbutazone / blood
- Phenylbutazone / metabolism
- Phenylbutazone / pharmacokinetics
- Phenylbutazone / urine
Citations
This article has been cited 2 times.- Khalil RH, Al-Humadi N. Types of acute phase reactants and their importance in vaccination. Biomed Rep 2020 Apr;12(4):143-152.
- Mills PC, Ng JC, Auer DE. The effect of the acute-phase response on in vitro drug metabolism and plasma protein binding in the horse. Vet Res Commun 1997 Jul;21(5):361-8.
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