Synovial distribution of “systemically” administered acetylsalicylic acid in the isolated perfused equine distal limb.
Abstract: This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plasma concentrations obtained from literature.Salicylate concentrations in the joint were determined using microdialysis and high performance liquid chromatography (HPLC). Any anti-inflammatory effect of synovial ASA concentrations was assessed using an ASA EC50 (half maximal effective concentration) determined in equine whole blood. Results: The ASA concentration in the synovial fluid (n=6) reached a maximum of 4 μg/mL, the mean concentration over the entire perfusion period was 2 μg/mL. Maximum SA concentration was 17 μg/mL, the average was 14 μg/mL. ASA and SA concentration in the synovial fluid exceeded systemic concentrations 2 h and 3.5 h after "systemic" administration, respectively. Conclusions: ASA and SA accumulated in the in the synovial fluid of the ex vivo model despite decreasing systemic concentrations. This suggests a prolonged anti-inflammatory effect within the joint that remains to be further elucidated.
Publication Date: 2013-03-26 PubMed ID: 23531229PubMed Central: PMC3617046DOI: 10.1186/1746-6148-9-56Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research focuses on how acetylsalicylic acid (ASA), also known as aspirin, and its byproduct, salicylic acid (SA), are distributed in horse joint fluid (synovial fluid) following systemic administration of the drug. This provides insights into potential prolonged anti-inflammatory effects of ASA within the joint.
Objective and Methodology
- The study’s objective was to understand how ASA and SA concentrations are distributed in the synovial fluid of the equine fetlock joint after ASA has been administered systemically. This research is of particular interest in the domain of equine sports where SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist in a horse’s plasma and urine.
- To study this, the researchers used an isolated perfused equine distal limb (a portion of a horse’s limb that’s been surgically removed but kept alive through artificial perfusion) rather than conducting an in-vivo (within the living) experiment. This method allows for more controlled and ethical testing.
- The team used microdialysis (a method that lets researchers sample the biochemical makeup of tissues) and high performance liquid chromatography (a technique for separating, identifying, and quantifying compounds) to measure the synovial concentrations of salicylates (the family of compounds that ASA and SA belong to).
- Any potential anti-inflammatory effect of synovial ASA was determined by assessing how much ASA is needed to achieve half the maximal response, a measure known as the EC50.
Findings
- In the six samples they studied, they found that the highest concentration of ASA in the synovial fluid was 4 μg/mL, with an average concentration of 2 μg/mL for the entire perfusion period.
- The highest concentration of SA was 17 μg/mL, with an average concentration of 14 μg/mL.
- Interestingly, the researchers noted that ASA and SA concentrations in the synovial fluid exceeded those in the systemic administration 2 and 3.5 hours after, respectively.
Conclusions and Implications
- The research found that ASA and its byproduct SA were present in increased concentrations in the synovial fluid, even as systemic concentrations decreased.
- This suggests ASA may have a lasting anti-inflammatory effect within the joint, an aspect that needs further investigation. Such findings have potential implications for understanding how ASA works and could inform better pain management strategies, particularly in the field of equine sports medicine.
Cite This Article
APA
Friebe M, Schumacher S, Stahl J, Kietzmann M.
(2013).
Synovial distribution of “systemically” administered acetylsalicylic acid in the isolated perfused equine distal limb.
BMC Vet Res, 9, 56.
https://doi.org/10.1186/1746-6148-9-56 Publication
Researcher Affiliations
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, Hannover, 30559, Germany. maren.friebe@tiho-hannover.de
MeSH Terms
- Administration, Intravenous / veterinary
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- Anti-Inflammatory Agents, Non-Steroidal / analysis
- Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
- Aspirin / administration & dosage
- Aspirin / analysis
- Aspirin / pharmacokinetics
- Chromatography, High Pressure Liquid / veterinary
- Female
- Hemoperfusion / veterinary
- Hindlimb
- Horses
- Male
- Microdialysis / veterinary
- Salicylic Acid / analysis
- Synovial Fluid / chemistry
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Citations
This article has been cited 1 times.- Buntenkötter K, Osmers M, Schenk I, Schänzer W, Machnik M, Düe M, Kietzmann M. Pharmacokinetics and in vitro efficacy of salicylic acid after oral administration of acetylsalicylic acid in horses.. BMC Vet Res 2017 Jan 19;13(1):28.
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