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Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses.
Abstract: Pain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics and local complications associated with using the NSAID phenylbutazone (PBZ) for IVRLP in six standing adult horses. Unassigned: PBZ-IVRLP, at a dose of 2.2 mg/kg PBZ, was performed in a randomly assigned forelimb cephalic vein in 6 standing, healthy adult horses. A placebo-IVRLP was performed in the contralateral forelimb for comparison. Systemic serum and radiocarpal joint synovial fluid PBZ concentrations were identified at various timepoints (before IVRLP T-0 h, just after tourniquet removal T-0.5, 1.5, 3, 5, 12, 16, and 24 h post IVRLP) for non-compartmental pharmacokinetic analysis and concentration over time curves. Local complications associated with PBZ-IVRP were evaluated for up to 7 days following PBZ-IVRLP using physical and ultrasonographic assessment. On day 7 horses were humanely euthanized with histology performed on both forelimbs at PBZ-IVRLP and placebo-IVRLP administration sites. Unassigned: Non-compartmental pharmacokinetics for PBZ, and its major metabolite oxyphenbutazone (OBZ), were determined for serum and synovial fluid. Synovial PBZ concentrations (mean ± SD; 1.9 ± 2.1 μg/mL) were significantly lower (p = 0.03; CI,0.46-7.36) than serum PBZ concentrations (5.8 ± 5.1 μg/mL) at any time point. Physical and ultrasonographic measurements were not significantly different between PBZ- and placebo-IVRLP forelimbs. The most common histologic findings included focal deep dermal/subcutaneous hemorrhage and edema. Two horses showed perivasculitis and one horse showed a resolving thrombus in the cephalic vein of the PBZ-IVRLP limb. This horse also had severe perivasculitis and fibrinosuppurative dermatitis/panniculitis in the placebo-IVRLP limb. Unassigned: PBZ-IVRLP pharmacokinetics at a 2.2 mg/kg dose showed no benefit compared to systemic PBZ administration in standing adult horses. Local complications associated with PBZ-IVRLP were similar to placebo-IVRLP on physical and ultrasonographic evaluation.
Copyright © 2023 O’Brien, Mochel, Kersh, Wang and Troy.
Publication Date: 2023-08-24 PubMed ID: 37691633PubMed Central: PMC10484477DOI: 10.3389/fvets.2023.1236976Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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This research study analyzed the effect of a pain-relief drug, phenylbutazone (PBZ), on horses when administered through intravenous regional limb perfusion (IVRLP). The intent was to understand the drug’s concentration in the horses’ joint fluids and the local complications that might occur with its use. The results showed no significant advantages over the use of systemic, or full-body, administration of the drug.
Research Objectives and Methodology
- The main aim of this study was to understand the pharmacological effects of the non-steroidal anti-inflammatory drug (NSAID), phenylbutazone, when delivered via IVRLP, a localized administration technique in horses. This method was thought to be potentially less harmful than systemic (whole body) administration, which can cause negative gastrointestinal and kidney effects.
- This study involved six healthy adult horses. In each horse, one forelimb was randomly selected for PBZ-IVRLP treatment, while the other received a placebo treatment for comparison. The concentration of PBZ in the blood and joint fluid was measured at several timepoints after the treatment.
- Local complications related to the treatment were monitored and evaluated for up to 7 days, using both physical examination and ultrasound imaging. Post-mortem histology (microscopic study of tissue structure) was performed on both forelimbs at the treatment sites after the horses were euthanized on the seventh day.
Research Findings
- The pharmacokinetic analysis showed lower PBZ concentration in the joint fluid compared to the blood at any given time point. This suggests that the drug was not as effectively targeted to the joint tissue as hoped with this localized administration technique.
- Physical and ultrasound assessments found no significant differences between the treated and placebo limbs, suggesting that PBZ-IVRLP treatment did not cause drastic changes or complications at the site of drug administration.
- However, various local complications were identified via post-mortem histological analysis. These included hemorrhage and edema (swelling), perivasculitis (inflammation around blood vessels), and a resolving blood clot in one horse’s treatment limb, while another horse showed severe inflammation and infection (fibrinosuppurative dermatitis/panniculitis) in the placebo limb.
Conclusions
- The study concluded that administering PBZ via IVRLP at a dose of 2.2mg/kg showed no significant advantage over systemic administration as far as the concentration of the drug in the joint fluid was concerned.
- The occurrence of local complications in both the treated and placebo limbs also suggests that the method of administration might not be any safer or less harmful than whole-body treatment.
Cite This Article
APA
O'Brien M, Mochel JP, Kersh K, Wang C, Troy J.
(2023).
Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses.
Front Vet Sci, 10, 1236976.
https://doi.org/10.3389/fvets.2023.1236976 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
- Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
- Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
- College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
- Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
- Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
- Department of Statistics, Iowa State University, Ames, IA, United States.
- Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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