Pharmacokinetics of single-dose cefuroxime in porcine intervertebral disc and vertebral cancellous bone determined by microdialysis

• Published in: The spine journal 2016-03, Vol.16 (3), p.432-438
• Main Authors: Hanberg, Pelle, MD-student, Bue, Mats, MD-student, PhD-student, Birke Sørensen, Hanne, MD, PhD, Søballe, Kjeld, Professor, MD, DMSc, Tøttrup, Mikkel, MD, PhD
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacokinetics; Cefuroxime; Cefuroxime - pharmacokinetics; Cervical Vertebrae - chemistry; Female; Infusions, Intravenous; Intervertebral disc; Intervertebral Disc - chemistry; Microbial Sensitivity Tests; Microdialysis; Models, Animal; Orthopedics; Pharmacokinetics; Subcutaneous Fat - chemistry; Swine; Tissue penetration; Vertebra
• ISSN: 1529-9430; 1878-1632
• DOI: 10.1016/j.spinee.2015.11.031

Abstract Background Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations. Purpose The objective of this study was to assess the C3–C4 intervertebral disc (IVD), C3 vertebral body cancellous bone, and subcutaneous adipose tissue (SCT) pharmacokinetics of cefuroxime by use of microdialysis in a large animal model. Study Design This was a single-dose, dense sampling large animal study of cefuroxime spine penetration. Methods Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 minutes. Measurements of cefuroxime were obtained from plasma, SCT, vertebral cancellous bone, and IVD for 8 hours thereafter. Microdialysis was applied for sampling in solid tissues. Results For both IVD and vertebral cancellous bone, the area under the concentration curve from zero to the last measured value (AUC0–last ) was significantly lower than that of free plasma. As estimated by the ratio of tissue AUC0–last to plasma AUC0–last , tissue penetration (95% confidence interval) of cefuroxime was significantly incomplete for the IVD 0.78 (0.57; 0.99), whereas for vertebral cancellous bone 0.78 (0.51; 1.04) and SCT 0.94 (0.73; 1.15) it was not. The penetration of cefuroxime from plasma to the IVD was delayed, and the maximal concentration and the elimination of cefuroxime were also reduced compared with both SCT and vertebral cancellous bone. Because of this delay in elimination of cefuroxime, the time with concentrations above the minimal inhibitory concentration (T>MIC ) was significantly longer in the IVD compared with the remaining compartments up to MICs of 6 µg/mL. Conclusions Microdialysis was successfully applied for serial assessment of the concentration of cefuroxime in the IVD and the vertebral cancellous bone. Penetration of cefuroxime from plasma to IVD was found to be incomplete and delayed, but because of a prolonged elimination, superior T>MIC was found in the IVD up to MICs of 6 µg/mL.