Pharmacokinetics and Pharmacodynamics of Enrofloxacin and Low-dose Amikacin after Regional Intravenous Limb Perfusion in Standing Horses

Abstract

Objective - To evaluate the tisular pharmacokinetics/dynamics of enrofloxacin and low-dose amikacin after regional intravenous limb perfusion (RILP) in standing horses. Animals – Fourteen adult horses Procedures – Enrofloxacin (1.5mg/kg, 7 horses) or 250 mg of amikacin (7 horses) were randomly infused by RILP in the front limb of standing horses. Capillary ultrafiltration devices were implanted in the subcutaneous tissue (ST) and bone marrow (BM) of the third metacarpal bone for collection of interstitial fluid. Samples were obtained from the serum, synovial fluid of the radiocarpal joint, interstitial fluid of ST and BM, prior to tourniquet release (time 0) and at 0.5, 1, 4, 8, 12, 24, and 36 hours. Concentrations of amikacin were detected by fluorescence polarization immunoassay and enrofloxacin concentrations were detected by high pressure liquid chromatography. Pharmacokinetic/pharmacodynamics analysis of tissue concentrations were measured and calculated using an MIC = 16 µg/ml for amikacin and =0.5 µg/ml for enrofloxacin. Results – Capillary ultrafiltration probes were effective in the collection of interstitial fluid samples for analysis. Three horses developed vasculitis after RILP with enrofloxacin. For both antimicrobials, the synovial fluid sample at time 0 attained the highest concentration (enrofloxacin - (Median (Range) 13.22 (0.254 - 167.9) µg/ml), (amikacin 26.2, (5.78 - 50.0) µg/ml). For enrofloxacin, therapeutic tissue concentrations above the MIC were maintained for approximately 24 hours in the ST and synovial fluid, and for 36 hours for the BM. For amikacin, therapeutic tissue concentrations above the MIC90 were not detected after perfusion. Pharmacodynamic variables for enrofloxacin indicated effective therapeutic concentrations for all the tissues. Conclusions and Clinical Relevance – Administration of 1.5 mg/kg of enrofloxacin by RILP should be considered as an alternative for treatment of equine orthopedic infections. However, care must be taken during administration. A higher dose of amikacin (>250 mg) is recommended for effective tissue concentrations after RILP in standing horses.