Effect of Experimentally Induced Synovitis on Amikacin Concentrations after Intravenous Regional Limb Perfusion

Objectives
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).
Study Design
Randomized crossover experimental design.
Animals
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 (Tmax; 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 (Cmax) 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 Cmax: 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.
Conclusion
Synovitis of the radiocarpal joint resulted in an earlier observed Tmax and higher observed Cmax of intra-articular amikacin after IVRLP compared with normal joints.