title: Plasma, subcutaneous tissue and bone concentrations of ceftiofur sodium after regional limb perfusion in horses.
abstract: BACKGROUND
  Regional limb perfusion (RLP) is an effective treatment option for injuries and infections of the distal limb in horses. Using ceftiofur sodium in RLP has been studied due to its superior spectrum of Gram-positive organisms compared to aminoglycosides, but it is not known if this antimicrobial drug adequately penetrates subcutaneous tissue and bone.
  
  
  OBJECTIVE
  To determine the concentration of ceftiofur in plasma, subcutaneous tissue and bone in horses after RLP.
  
  
  METHODS
  Experimental prospective study.
  
  
  METHODS
  Six healthy horses were used in this study. Under standing sedation, an Esmarch tourniquet was applied to both proximal metacarpi and RLP was performed in each forelimb by injecting either ceftiofur sodium (experimental limb) or saline (control limb) i.v. in the lateral palmar digital vein. The experimental limb was injected with 2 g ceftiofur diluted to 60 mL with sterile saline. The control limb was injected with 60 mL of sterile saline. The tourniquet was left in place for 30 min post injection. Plasma, subcutaneous tissue and cortical bone samples were collected immediately after tourniquet removal (0.5 h), 12 and 24 h post injection. Ceftiofur concentrations and its active metabolite desfuroylceftiofur were analysed using high performance liquid chromatography-tandem mass spectrometry and the results were compared between control and experimental limbs using a Wilcoxon signed rank test.
  
  
  RESULTS
  The median plasma concentrations were greater than the minimum inhibitory concentration (MIC) for common pathogens (1 μg/mL) at 0 and 12 h post RLP. The median subcutaneous tissue concentrations were greater than MIC (1 μg/g) at all 3 time points in the experimental limb. The median bone concentration was above MIC (1 μg/g) at time 0 in the experimental limb but was below MIC at 12 and 24 h in the experimental limb.
  
  
  CONCLUSIONS
  Ceftiofur administration via RLP maintained plasma concentrations above MIC for 12 h. Subcutaneous tissue concentrations above MIC were maintained for 24 h. Bone concentrations were only above MIC immediately after tourniquet removal. Further research is needed to evaluate ceftiofur administration via RLP and its implications in disease states.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Cox
authors.affiliation: Gail Holmes Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Nelson
authors.affiliation: Flint Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wittenburg
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Gold
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism*; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005552:Forelimb; D006736:Horses / Q000097:blood* / Q000378:metabolism; D008297:Male; D012039:Regional Blood Flow; D040521:Subcutaneous Tissue / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C053503:ceftiofur
keywords: antimicrobial drug; horse