title: Effect of experimentally induced synovitis on amikacin concentrations after intravenous regional limb perfusion.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, 501 D W Brooks Drive, Athens, GA 30602, USA. varela@uga.edu
authors.forename: Axel M
authors.initials: AM
authors.lastname: Beccar-Varela
authors.forename: Kira L
authors.initials: KL
authors.lastname: Epstein
authors.forename: Catherine L
authors.initials: CL
authors.lastname: White
mesh_terms: D000583:Amikacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006736:Horses; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000633:toxicity; D013585:Synovitis / Q000139:chemically induced* / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D000583:Amikacin