Population pharmacokinetics of cefuroxime and uptake into hip and spine bone of patients undergoing orthopaedic surgery.

Abstract

To reduce the incidence of peri- or postoperative infections in orthopaedic surgery, patients are prophylactically treated with antibiotics. Here, we wanted to know whether effective bone and intervertebral disc concentrations of cefuroxime are reached. Patients undergoing surgery of hip (N=40; 62.5% male) or spine (N=40; 55% male) were pretreated with 1.5g of the second-generation cephalosporin cefuroxime before surgery. We studied plasma population kinetics and bone and intervertebral disc (C5/6 till L5/S1) concentrations of cefuroxime using high-performance liquid chromatography. The plasma kinetics of cefuroxime in 80 patients was analysed using a population approach. The clearance amounted to 7.86l/h. The peripheral and central volumes of distribution were estimated as 8.45 and 10.4l, respectively. The concentrations in hip samples amounted to 9.8±0.6µg/g in cancellous bone and 8.9±0.8µg/g in cortical bone. Cefuroxime concentrations in vertebral bone and intervertebral discs were calculated as 9.6±1.3 and 8.9±1.1µg/g, respectively. Even if a majority of patients undergoing hip or spine surgery probably achieved adequate concentrations of cefuroxime, not all patients reached bone concentrations of cefuroxime above a recommended breakpoint for susceptible germs at the time of surgery.