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Pharmacokinetics and pharmacodynamics of enrofloxacin and a low dose of amikacin administered via regional intravenous limb perfusion in standing horses

Alberto Parra-Sanchez MVZ1, Joel Lugo DVM, MS2, Dawn M. Boothe DVM, PhD3, Earl M. Gaughan DVM4, R. Reid Hanson DVM5, Sue Duran RPh, PhD6, and James K. Belknap DVM, PhD7
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  • 1 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 3 Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 4 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 5 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 6 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 7 Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

Abstract

Objective—To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses.

Animals—14 adult horses.

Procedures—Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint were collected prior to (time 0) and at intervals after tourniquet release for determination of drug concentrations. For pharmacokinetic-pharmacodynamic analyses, minimum inhibitory concentrations (MICs) of 16 μg/mL (amikacin) and 0.5 μg/mL (enrofloxacin) were applied.

Results—After RILP with enrofloxacin, 3 horses developed vasculitis. The highest synovial fluid concentrations of enrofloxacin and amikacin were detected at time 0; median values (range) were 13.22 μg/mL (0.254 to 167.9 μg/mL) and 26.2 μg/mL (5.78 to 50.0 μg/mL), respectively. Enrofloxacin concentrations exceeded MIC for approximately 24 hours in STIF and synovial fluid and for 36 hours in BMIF. After perfusion of amikacin, concentrations greater than the MIC were not detected in any samples. Effective therapeutic concentrations of enrofloxacin were attained in all samples.

Conclusions and Clinical Relevance—In horses with orthopedic infections, RILP of enrofloxacin (1.5 mg/kg) should be considered as a treatment option. However, care must be taken during administration. A dose of amikacin > 250 mg is recommended to attain effective tissue concentrations via RILP in standing horses.

Abstract

Objective—To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses.

Animals—14 adult horses.

Procedures—Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint were collected prior to (time 0) and at intervals after tourniquet release for determination of drug concentrations. For pharmacokinetic-pharmacodynamic analyses, minimum inhibitory concentrations (MICs) of 16 μg/mL (amikacin) and 0.5 μg/mL (enrofloxacin) were applied.

Results—After RILP with enrofloxacin, 3 horses developed vasculitis. The highest synovial fluid concentrations of enrofloxacin and amikacin were detected at time 0; median values (range) were 13.22 μg/mL (0.254 to 167.9 μg/mL) and 26.2 μg/mL (5.78 to 50.0 μg/mL), respectively. Enrofloxacin concentrations exceeded MIC for approximately 24 hours in STIF and synovial fluid and for 36 hours in BMIF. After perfusion of amikacin, concentrations greater than the MIC were not detected in any samples. Effective therapeutic concentrations of enrofloxacin were attained in all samples.

Conclusions and Clinical Relevance—In horses with orthopedic infections, RILP of enrofloxacin (1.5 mg/kg) should be considered as a treatment option. However, care must be taken during administration. A dose of amikacin > 250 mg is recommended to attain effective tissue concentrations via RILP in standing horses.

Contributor Notes

Dr. Belknap's present address is Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Supported by the Birmingham Racing Commission.

Presented at the ACVS Resident Forum, San Diego, October 2005 and at the 2nd Annual World Veterinary Orthopedic Congress, Keystone, Colo, February 2006.

Address correspondence to Dr. Lugo.