title: Pharmacokinetics of cefuroxime in porcine cortical and cancellous bone determined by microdialysis.
abstract: Traditionally, the pharmacokinetics of antimicrobials in bone have been investigated using bone biopsy specimens, but this approach suffers from considerable methodological limitations. Consequently, new methods are needed. The objectives of this study were to assess the feasibility of microdialysis (MD) for measuring cefuroxime in bone and to obtain pharmacokinetic profiles for the same drug in porcine cortical and cancellous bone. The measurements were conducted in bone wax sealed and unsealed drill holes in cortical bone and in drill holes in cancellous bone and in subcutaneous tissue. As a reference, the free and total plasma concentrations were also measured. The animals received a bolus of 1,500 mg cefuroxime over 30 min. No significant differences were found between the key pharmacokinetic parameters for sealed and unsealed drill holes in cortical bone. The mean ± standard error of the mean area under the concentration-time curve (AUC) values from 0 to 5 h were 6,013 ± 1,339, 3,222 ± 1086, 2,232 ± 635, and 952 ± 290 min · μg/ml for free plasma, subcutaneous tissue, cancellous bone, and cortical bone, respectively (P < 0.01, analysis of variance). The AUC for cortical bone was also significantly different from that for cancellous bone (P = 0.04). This heterogeneous tissue distribution was also reflected in other key pharmacokinetic parameters. This study validates MD as a suitable method for measuring cefuroxime in bone. Cefuroxime penetration was impaired for all tissues, and bone may not be considered one distinct compartment.
authors.affiliation: Department of Orthopaedic Surgery, Hospital Unit Horsens, Horsens, Denmark Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark mikkel.tottrup@ki.au.dk.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Tøttrup
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Tore Forsingdal
authors.initials: TF
authors.lastname: Hardlei
authors.affiliation: Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Bendtsen
authors.affiliation: Department of Orthopaedic Surgery, Hospital Unit Horsens, Horsens, Denmark Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mats
authors.initials: M
authors.lastname: Bue
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
authors.affiliation: Statens Serum Institute, Copenhagen, Denmark.
authors.forename: Kurt
authors.initials: K
authors.lastname: Fuursted
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kjeld
authors.initials: K
authors.lastname: Søballe
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Birke-Sørensen
mesh_terms: D000465:Algorithms; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism*; D002444:Cefuroxime / Q000493:pharmacokinetics*; D017551:Microdialysis; D040521:Subcutaneous Tissue / Q000378:metabolism; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D002444:Cefuroxime