title: Single-dose pharmacokinetics of vancomycin in porcine cancellous and cortical bone determined by microdialysis.
abstract: High treatment failure rates and the need for prolonged antimicrobial therapy for osteomyelitis and implant-associated infections suggest that antimicrobial bone penetration may be incomplete. Assessment of the bone pharmacokinetics of antimicrobials is challenged by a lack of validated methods. In this study, 1000 mg of vancomycin was administered as a single dose over 100 min to eight female pigs. Plasma, subcutaneous adipose tissue (SCAT) and bone pharmacokinetics were investigated over 12 h. Microdialysis was applied for collection of samples in bone and SCAT. The vancomycin concentration in microdialysates was determined using ultra-high performance liquid chromatography, whilst the free plasma concentration was determined using Cobas c501. The mean (95% CI) area under the concentration-time curve (AUC(0-last); minμg/mL) was 9375 (7445-11304), 9304 (7374-11233), 5998 (3955-8040) and 3451 (1522-5381) for plasma, SCAT, and cancellous and cortical bone, respectively (ANOVA P-value < 0.001). Both cortical and cancellous bone AUC0-last were lower than that of free plasma (P < 0.01). Peak drug concentrations (C(max)) in cortical and cancellous bone were also significantly lower than that of free plasma (P < 0.001). Moreover, both AUC(0-last) and C(max) were significantly lower in cortical bone than in cancellous bone (P < 0.025). Bone penetration of vancomycin was found to be incomplete and delayed. Significant differences in pharmacokinetics between cancellous and cortical bone suggest that bone may not be considered as one compartment. Future studies should focus on validating the applicability of microdialysis for assessment of antimicrobial bone pharmacokinetics.
authors.affiliation: Department of Orthopaedic Surgery, Horsens Regional Hospital, Horsens, Denmark; Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark. Electronic address: matsbue@clin.au.dk.
authors.forename: Mats
authors.initials: M
authors.lastname: Bue
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Birke-Sørensen
authors.affiliation: Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Theis M
authors.initials: TM
authors.lastname: Thillemann
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Tore F
authors.initials: TF
authors.lastname: Hardlei
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: Department of Orthopaedic Surgery, Horsens Regional Hospital, Horsens, Denmark; Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Tøttrup
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D017551:Microdialysis; D010949:Plasma / Q000737:chemistry; D050151:Subcutaneous Fat / Q000737:chemistry; D013552:Swine; D014640:Vancomycin / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Bone; Microdialysis; Pharmacokinetics; Tissue penetration; Vancomycin