Predictive performance of pharmacokinetic models for target concentration-controlled infusion of cefoxitin as a prophylactic antibiotic in patients with colorectal surgery

We aimed to evaluate the predictive performance of previously constructed free
(Cfree) and total (Ctotal) cefoxitin pharmacokinetic models and the possibility of administering
cefoxitin via the target-controlled infusion (TCI) method in clinical practice.
Two external validation studies (N = 31 for Cfree model, N = 30 for Ctotal model)
were conducted sequentially. Cefoxitin (2 g) was dissolved in 50 mL of normal saline
to give a concentration of 40 mg mL-1. Before skin incision, cefoxitin was infused
with a TCI syringe pump. Target concentrations of free concentration and total concentration
were set to 25 and 80 μg mL-1, respectively, which were administered
throughout the surgery. Three arterial blood samples were collected to measure the
total and free plasma concentrations of cefoxitin at 30, 60 and 120 min, after the
start of cefoxitin administration. The predictive performance was evaluated using
four parameters: inaccuracy, divergence, bias and wobble. The pooled median (95%
confidence interval) biases and inaccuracies were - 45.9 (-47.3 to -44.5) and 45.9
(44.5 to 47.3) for Cfree model (Choi_F model), and - 16.6 (-18.4 to -14.8) and 18.5
(16.7 to 20.2) for Ctotal model (Choi_Told model), respectively. The predictive performance
of the newly constructed model (Choi_Tnew model), developed by adding the
total concentration data measured in the external validation, was better than that of
the Choi_Told model. Models constructed with total concentration data were suitable
for clinical use. Administering cefoxitin using the TCI method in patients maintained
the free concentration above the minimal inhibitory concentration (MIC) breakpoints
of the major pathogens causing surgical site infection throughout the operation
period.