title: Pharmacokinetics of single-dose cefuroxime in porcine intervertebral disc and vertebral cancellous bone determined by microdialysis.
abstract: BACKGROUND
  Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations.
  
  
  OBJECTIVE
  The objective of this study was to assess the C3-C4 intervertebral disc (IVD), C3 vertebral body cancellous bone, and subcutaneous adipose tissue (SCT) pharmacokinetics of cefuroxime by use of microdialysis in a large animal model.
  
  
  METHODS
  This was a single-dose, dense sampling large animal study of cefuroxime spine penetration.
  
  
  METHODS
  Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 minutes. Measurements of cefuroxime were obtained from plasma, SCT, vertebral cancellous bone, and IVD for 8 hours thereafter. Microdialysis was applied for sampling in solid tissues.
  
  
  RESULTS
  For both IVD and vertebral cancellous bone, the area under the concentration curve from zero to the last measured value (AUC(0-last)) was significantly lower than that of free plasma. As estimated by the ratio of tissue AUC(0-last) to plasma AUC(0-last), tissue penetration (95% confidence interval) of cefuroxime was significantly incomplete for the IVD 0.78 (0.57; 0.99), whereas for vertebral cancellous bone 0.78 (0.51; 1.04) and SCT 0.94 (0.73; 1.15) it was not. The penetration of cefuroxime from plasma to the IVD was delayed, and the maximal concentration and the elimination of cefuroxime were also reduced compared with both SCT and vertebral cancellous bone. Because of this delay in elimination of cefuroxime, the time with concentrations above the minimal inhibitory concentration (T(>MIC)) was significantly longer in the IVD compared with the remaining compartments up to MICs of 6 µg/mL.
  
  
  CONCLUSIONS
  Microdialysis was successfully applied for serial assessment of the concentration of cefuroxime in the IVD and the vertebral cancellous bone. Penetration of cefuroxime from plasma to IVD was found to be incomplete and delayed, but because of a prolonged elimination, superior T(>MIC) was found in the IVD up to MICs of 6 µg/mL.
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Tage-Hansens Gade 2, Bygning 9A, 8000 Aarhus C, Denmark. Electronic address: pellehanberg@hotmail.com.
authors.forename: Pelle
authors.initials: P
authors.lastname: Hanberg
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Tage-Hansens Gade 2, Bygning 9A, 8000 Aarhus C, Denmark; Department of Orthopaedic Surgery, Horsens Regional Hospital, Sundvej 30, 8700 Horsens, Denmark.
authors.forename: Mats
authors.initials: M
authors.lastname: Bue
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Tage-Hansens Gade 2, Bygning 9A, 8000 Aarhus C, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Birke Sørensen
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Tage-Hansens Gade 2, Bygning 9A, 8000 Aarhus C, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Søballe
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Tage-Hansens Gade 2, Bygning 9A, 8000 Aarhus C, Denmark; Department of Orthopaedic Surgery, Randers Regional Hospital, Skovlyvej 1, 8930 Randers NØ, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Tøttrup
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002444:Cefuroxime / Q000493:pharmacokinetics*; D002574:Cervical Vertebrae / Q000737:chemistry*; D005260:Female; D007262:Infusions, Intravenous; D007403:Intervertebral Disc / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D017551:Microdialysis; D023421:Models, Animal; D050151:Subcutaneous Fat / Q000737:chemistry*; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D002444:Cefuroxime
keywords: Cefuroxime; Intervertebral disc; Microdialysis; Pharmacokinetics; Tissue penetration; Vertebra