Effect of experimentally induced synovitis on amikacin concentrations after intravenous regional limb perfusion.
Abstract: To determine the effects of experimentally induced synovitis of the radiocarpal joint on the intra-articular pharmacokinetics and pharmacodynamics of amikacin after intravenous regional limb perfusion (IVRLP). Methods: Randomized crossover experimental design. Methods: Adult horses (n = 8). Methods: Horses were randomly assigned into 2 trials: synovitis and no-synovitis. Radiocarpal joint synovitis was induced with lipopolysaccharide 6 hours before IVRLP. IVRLP (5-mg/kg amikacin qs 60 mL) was performed with a pneumatic tourniquet under general anesthesia. Synovial fluid was obtained before and 0.5, 1, 3, 5, 12, 24, 48 hours after IVRLP. Amikacin concentrations at each time point and pharmacokinetic values were compared between synovitis and no-synovitis trials with Student's t-test. Results: Amikacin synovial fluid concentrations indicated suspected tourniquet failure on 3 occasions (2 synovitis, 1 no-synovitis) on 3 different horses. Data from both trials in these 3 horses were excluded from further analysis. Observed time to maximal concentration (T(max); mean ± SD = 54 ± 13.42 min) was reached earlier in synovitis joints (5/5, 30 min) than in no-synovitis joints (1/5, 30 min and 4/5, 1 h; P = .0476) (P = .0161). Mean observed maximal concentration (C(max)) was higher in synovitis joints (144.48 ± 43.17 μg/mL) than in no-synovitis joints (60.02 ± 28.81 μg/mL; P = .0301). The recommended C(max): minimum inhibitory concentration ratio of 8 was achieved in 3/5 of the successfully perfused joints with induced synovitis, but this ratio was not achieved in any of the clinically normal joints. Conclusions: Synovitis of the radiocarpal joint resulted in an earlier observed T(max) and higher observed C(max) of intra-articular amikacin after IVRLP compared with normal joints.
© Copyright 2011 by The American College of Veterinary Surgeons.
Publication Date: 2011-09-08 PubMed ID: 22380674DOI: 10.1111/j.1532-950X.2011.00875.xGoogle Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
Summary
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The research studied the impact of experimentally induced synovitis (inflammation of the joint lining) on the effects and distribution of amikacin, an antibiotic, within the joint after intravenous regional limb perfusion (blood supply to a limb) in horses. The findings showed that synovitis results in an earlier occurrence of maximum drug concentration and a higher maximum drug concentration than in normal joints.
Methodology
- The study used a randomized crossover experimental design on eight adult horses.
- These horses were randomly assigned to two trials – one with induced synovitis (inflammation of the joint lining) and the other without synovitis.
- The inflammation in the radiocarpal joint (the equivalent of the human wrist joint) was induced with lipopolysaccharide six hours before intravenous regional limb perfusion (IVRLP) – a procedure performed under general anesthesia where a tourniquet is applied to a limb to restrict blood flow and a drug is administered to the limb.
- Synovial fluid was obtained before the procedure and at various time points post-procedure. The concentration of the drug amikacin in the joint fluid at each time point and the drug’s pharmacokinetic values (how the drug is absorbed, distributed, metabolized, and excreted) were compared between the synovitis and no-synovitis trials using a statistical method known as the Student’s t-test.
Results
- The researchers found suspected instances of tourniquet failure (an instance where the tourniquet does not successfully restrict the blood flow in a limb) in three horses. The results from these horses were not included in further analysis.
- The time to reach the maximum drug concentration was earlier in joints with synovitis than those without. Additionally, the average maximum drug concentration was higher in joints with induced synovitis than in normal joints.
- In terms of achieving the therapeutic threshold (recommended C(max): minimum inhibitory concentration ratio of 8), the induction of synovitis showed better outcomes, reaching the threshold in 3 out of 5 cases. None of the clinically normal joints were able to achieve this ratio.
Conclusions
- The results imply that synovitis of the radiocarpal joint results in an earlier and higher observed peak concentration of amikacin post-IVRLP compared to healthy joints. This suggests that disease conditions like inflammation can influence the efficacy of drug administration and treatment outcomes, particularly in the case of antimicrobial drugs like amikacin.
Cite This Article
APA
Beccar-Varela AM, Epstein KL, White CL.
(2011).
Effect of experimentally induced synovitis on amikacin concentrations after intravenous regional limb perfusion.
Vet Surg, 40(7), 891-897.
https://doi.org/10.1111/j.1532-950X.2011.00875.x Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, 501 D W Brooks Drive, Athens, GA 30602, USA. varela@uga.edu
MeSH Terms
- Amikacin / administration & dosage
- Amikacin / pharmacokinetics
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / pharmacokinetics
- Cross-Over Studies
- Horses
- Injections, Intravenous
- Lipopolysaccharides / toxicity
- Synovitis / chemically induced
- Synovitis / metabolism
- Time Factors
- Tissue Distribution
Citations
This article has been cited 6 times.- Guillot M, Mespoulhes-Rivière C, Bousquet-Mélou A, Lacroix MZ, Roques BB, Lallemand EA. Pharmacokinetics, pharmacodynamics, and local tolerance at injection site of penicillin and gentamicin administered by intravenous regional limb perfusion in standing horses: comparison between weightbearing and flexed limbs. BMC Vet Res 2025 Nov 7;21(1):650.
- Hardefeldt L, Thomas K, Page S, Norris J, Browning G, El Hage C, Stewart A, Gilkerson J, Muscatello G, Verwilghen D, van Galen G, Bauquier J, Cuming R, Reynolds B, Whittaker C, Wilkes E, Clulow J, Burden C, Begg L. Antimicrobial prescribing guidelines for horses in Australia. Aust Vet J 2025 Dec;103(12):781-889.
- Redding LE, Elzer EJ, Ortved KF. Effects of regional limb perfusion technique on concentrations of antibiotic achieved at the target site: A meta-analysis. PLoS One 2022;17(4):e0265971.
- Gustafsson K, Tatz AJ, Dahan R, Abu Ahmad W, Britzi M, Sutton GA, Kelmer G. Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses. Animals (Basel) 2021 Jul 13;11(7).
- Nieto JE, Trela J, Stanley SD, Yamout S, Snyder JR. Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses. Can J Vet Res 2016 Jul;80(3):230-5.
- Hyde RM, Lynch TM, Clark CK, Slone DE, Hughes FE. The influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion in the standing horse. Can Vet J 2013 Apr;54(4):363-7.
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