Traditionally, the pharmacokinetics of antimicrobials in bone have been investigated using bone biopsies, but this approach suffers from considerable methodological limitations. Consequently, new methods are needed. The objectives of this study were to assess the feasibility of the microdialysis (MD) technique for measurement of cefuroxime in bone, and to obtain pharmacokinetic profiles for the same drug in porcine cortical and cancellous bone. Measurements were conducted in bone-wax sealed and unsealed drill holes in cortical bone, in drill holes in cancellous bone and in subcutaneous tissue. As reference, free and total plasma concentrations were also measured. The animals received a bolus of 1500 mg cefuroxime over 30 min. No significant differences between key pharmacokinetic parameters for sealed and unsealed drill holes in cortical bone were found. The mean area under the concentration-time curves (AUC) from 0 to 5 hours were 6013±1339, 3222±1086, 2232±635 and 952±290 min μg/mL for free plasma, subcutaneous tissue, cancellous and cortical bone, respectively (ANOVA P < 0.01). AUC for cortical bone was also significantly different from that of cancellous bone (P = 0.04). The 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 as one distinct compartment.
Antimicrobial Agents and Chemotherapy, 2014, Vol 58, Issue 6, p. 3200-3205