Pharmacokinetics of Cefuroxime in Porcine Cortical and Cancellous Bone Determined by Microdialysis

Abstract

f 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 · g/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.

Continuous versus Short-Term Infusion of Cefuroxime: Assessment of Concept Based on Plasma, Subcutaneous Tissue, and Bone Pharmacokinetics in an Animal Model

“…In agreement with our previous study, the poorest tissue penetration was found for bone (15). Somewhat surprisingly, bone penetration in the CI group was poorer than in the STI group, but this seems partly compensated for by higher free plasma AUCs.…”

“…In a recent porcine study, we demonstrated substantially impaired bone and subcutaneous tissue (SCT) penetration of cefuroxime (15). The pharmacokinetic profiles suggested that EI or CI of the drug might attain increased time with tissue concentrations above the MIC (TϾMIC) for relevant microorganisms.…”

Different bone remodeling levels of trabecular and cortical bone in response to changes in Wnt/β‐catenin signaling in mice

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Distribution of clomipramine, citalopram, midazolam, and metabolites in skeletal tissue after chronic dosing in rats

“…Due to this structure, cancellous bone has a bigger contact surface area with vascularization and bone marrow compared to trabecular bone, which makes it more suitable for drug‐to‐bone interaction. This bigger contact surface explains the higher drug concentration found in the epiphysis compared to the diaphysis . The exact mechanism of how drugs are incorporated in skeletal tissue is still under discussion.…”

“…This bigger contact surface explains the higher drug concentration found in the epiphysis compared to the diaphysis. 7 The exact mechanism of how drugs are incorporated in skeletal tissue is still under discussion. A recent model gives a possible explanation for the incorporation of drugs into bone tissue.…”