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Journal of veterinary pharmacology and therapeutics2023; 46(4); 229-237; doi: 10.1111/jvp.13119

Pharmacokinetics of intra-articular buprenorphine in horses with lipopolysaccharide-induced synovitis.

Abstract: The objective of this study was to describe the pharmacokinetics of intra-articular (IA) administered buprenorphine in horses with lipopolysaccharide (LPS)-induced synovitis. Radiocarpal synovitis was induced in six healthy adult horses with the IA injection of LPS (0.5 ng/joint) on two occasions in a randomized cross-over design. Treatments (IA buprenorphine (IAB) at 5 μg/kg plus intravenous saline; and intravenous buprenorphine (IVB) at 5 μg/kg plus IA saline) were administered 4 h following LPS injection. Concentrations of buprenorphine were assessed in plasma and synovial fluid (SF) at 0.5, 2, 6, 12, and 24 h after administration. Pharmacokinetic parameters after IVB and IAB in plasma and synovial fluid were calculated using a nonlinear mixed effects model. IAB was detectable in SF of all horses at 24 h [median concentration of 6.2 (3.46-22.6) ng/mL]. IAB resulted in a median plasma concentration of 0.59 (0.42-1.68) ng/mL at 0.5 h and was detectable in all subjects for up to 6 h and in two horses for up to 12 h. IVB resulted in SF concentrations detected up to 6 h in all horses [median concentration of 0.12 (0.07-0.82) ng/mL]. Results suggest that IA buprenorphine remains present in the inflamed joint for at least 24 h and systemic absorption occurs.
© 2023 John Wiley & Sons Ltd.
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Publication Date: 2023-02-23 PubMed ID: 36815620DOI: 10.1111/jvp.13119Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research study examines how the drug buprenorphine, administered directly into the joint space (intra-articularly), behaves in horses that have a type of joint inflammation induced by lipopolysaccharide. The study aimed to understand how the drug is absorbed and metabolized and how long it stays within the joint and the bloodstream.

Study Design

  • The study is based on a type of joint inflammation in horses which is induced by lipopolysaccharide (LPS), a component of the cell walls of certain bacteria.
  • Synovitis, an inflammation of the synovium (a thin layer of tissue that lines the parts of joints), was triggered in six healthy adult horses through an intra-articular (inside the joint) injection of LPS.
  • This process was repeated two times using a randomly determined sequence, a method used to reduce the potential for bias in the results.

Treatment and Data Collection

  • The horses then received treatment 4 hours after the LPS injection in two forms: intra-articular buprenorphine with intravenous saline, and intravenous buprenorphine with intra-articular saline.
  • Researchers collected blood and joint fluid samples at specific intervals (0.5, 2, 6, 12, and 24 hours) after administering the treatments.
  • The concentration of buprenorphine in both the plasma and joint fluid was analyzed at these time points after administration.

Pharmacokinetic Analysis

  • To determine the pharmacokinetics of the drug (how the body absorbs, distributes, metabolizes, and excretes the drug), the team used a nonlinear mixed effects model.
  • They found that intra-articular buprenorphine could still be detected in the joint fluid 24 hours after administration in all horses.
  • The drug was also present in the blood plasma, with the concentration highest at 0.5 hours after administration. It could be detected for up to 6 hours in all subjects and up to 12 hours in two horses.
  • In contrast, buprenorphine that was given via intravenous administration could only be detected up to 6 hours post-administration in the joint fluid.

Conclusion

  • The study suggests that when buprenorphine is administered directly into the joint space in horses with LPS-induced inflammation, it remains in that localized area for an extended time, specifically, for at least 24 hours, which may allow for a sustained therapeutic effect in alleviating joint pain.
  • The researchers also suggest that some degree of systemic absorption (into the broader bloodstream) occurs as well but appears to decrease over time.

Cite This Article

APA
Castro-Cuellar G, Cremer J, Queiroz-Williams P, Knych HK, Leise BS. (2023). Pharmacokinetics of intra-articular buprenorphine in horses with lipopolysaccharide-induced synovitis. J Vet Pharmacol Ther, 46(4), 229-237. https://doi.org/10.1111/jvp.13119

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 46
Issue: 4
Pages: 229-237

Researcher Affiliations

Castro-Cuellar, Gabriel
  • Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Cremer, Jeannette
  • Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Queiroz-Williams, Patricia
  • Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Knych, Heather K
  • KL Maddy Equine Analytical Pharmacology Lab, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Leise, Britta S
  • Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.

MeSH Terms

  • Animals
  • Buprenorphine / therapeutic use
  • Horse Diseases / chemically induced
  • Horse Diseases / drug therapy
  • Horses
  • Injections, Intra-Articular / veterinary
  • Lipopolysaccharides
  • Synovial Fluid
  • Synovitis / chemically induced
  • Synovitis / drug therapy
  • Synovitis / veterinary

Grant Funding

  • Charles Cusimano EHSP grant
  • Louisiana State University School of Veterinary Medicine Charles V. Cusimano EHSV funding

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Citations

This article has been cited 2 times.
  1. Duggan MJS, Kearney C, Baltrimaite M, Labberté MC, Gibney R, Brama PAJ. Refinement of the Lipopolysaccharide-Induced Synovitis Model in Equine Middle Carpal Joints. Animals (Basel) 2025 Aug 22;15(17).
    doi: 10.3390/ani15172474pubmed: 40941269google scholar: lookup
  2. Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ. A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment. Animals (Basel) 2023 Oct 12;13(20).
    doi: 10.3390/ani13203190pubmed: 37893914google scholar: lookup
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