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· DOS Abstracts
Pharmacokinetics of vancomycin in porcine bone
obtained by microdialysis
Mats Bue, Hanne Birke-Sørensen, Theis Muncholm Thillemann, Kjeld Søballe,
Mikkel Tøttrup
Department of Orthopaedic Surgery, Hospital Unit Horsens; Orthopaedic
Research Unit, Aarhus University Hospital
Background:
Traditionally, the pharmacokinetics of antimicrobials in bone has
been investigated using bone biopsies, which suffers from considerable meth-
odological limitations. Microdialysis (MD) offers an attractive alternative to ob-
tain bone concentrations of antimicrobials.
Purpose / Aim of Study:
The aims of this study were to investigate the suit-
ability of the MD-method for vancomycin measurement in a laboratory setting
and to apply MD for measurement of vancomycin in subcutaneous tissue, can-
cellous and cortical bone.
Materials and Methods:
Laboratory studies were conducted to determine in
vitro recovery by gain and by loss (1-25 µg/ml), appropriate flow rate, calibra-
tion concentrations and the effect of temperature and concentration on re-
covery. In a porcine study MD-catheters were placed in subcutaneous tissue,
cancellous and cortical bone. CMA 63 catheters were used, and were in bone
placed in drill holes, made by use of a 2 mm drill. Blood samples were drawn from
a central venous catheter. CMA 107 pumps produced flow rates of 0.5 µl/min.
All dialysates were analysed with an UHPLC-method, and vancomycin concen-
trations in plasma were determined with cobas (c501, Roche). Verification of
catheter locations was performed by autopsy, and intra cortical placement of
drill holes was verified by post-mortem CT.
Findings / Results:
Laboratory study: Recovery by gain equalled recovery by
loss, and was independent of the concentration. Recovery increased slightly
with increasing temperature. Porcine study: For all extravascular tissue, a het-
erogeneous distribution was demonstrated. Significant differences in AUC were
found for bone, cancellous as well as cortical, when compared to free plasma.
The lowest AUC was found in cortical bone.
Conclusions:
MD is a reliable method for assessment of the penetration and
pharmacokinetics of vancomycin in bone and soft tissue.
161.
