Pharmacokinetics of ceftriaxone in plasma and bone of patients undergoing hip or knee surgery

Patients undergoing hip or knee replacement therapy are routinely pretreated with antibiotics before surgery. It is controversial in which antibiotic is the treatment of choice for this purpose. One possibility is the cephalosporin ceftriaxone. Here, we wanted to know if effective tissue concentrations are reached.

We studied plasma and bone kinetics of ceftriaxone in orthopaedic patients (n = 22) treated with ceftriaxone (2 g) immediately prior operation. Plasma samples were withdrawn before and at three time points after ceftriaxone infusion. After bone replacement, extracts from cancellous bone or cortical bone were obtained, and ceftriaxone was quantified using column chromatography.

The plasma kinetics of ceftriaxone and distribution into bone were analysed using a population approach (ADAPT 5). The population mean of the area under the curve (AUC) was 140 mg h/l. A cancellous bone to plasma concentration ratio of 1.12 ± 1.29 was achieved 5 h after start of infusion. The half-life of uptake into the cortical bone was less (8.4 h) than into cancellous bone (12.1 h, P < 0.05).

Under these experimental conditions, concentrations of ceftriaxone in cancellous and cortical bone should be adequate to protect the patients against usual ceftriaxone-sensitive nosocomial infections and are substantially lower than the plasma concentrations.