Development of a new pharmacokinetic model for target-concentration controlled infusion of cefoxitin as a prophylactic antibiotic in colorectal surgical patients

Abstract

Aims: There are several limitations to the existing method of administering cefoxitin as a prophylactic antibiotic, and the limitations may be overcome by applying the target-concentration controlled infusion (TCI) method. Population pharmacokinetic parameters are required to administer cefoxitin by the TCI method. The aim of this study was to construct a new pharmacokinetic model of cefoxitin for the TCI method in colorectal surgical patients Methods: In patients undergoing colorectal surgery, 2 g cefoxitin was dissolved in 50 mL saline and administered for 10 min prior to skin incision. Arterial blood samples were obtained at pre-set intervals to measure the total and free plasma concentrations of cefoxitin. Population pharmacokinetic analysis was performed using the NONMEM software (ICON Development Solutions, Dublin, Ireland). Additionally, the stochastic simulation was used to indirectly evaluate the effectiveness of the two administration methods (standard method vs. TCI) Results: In total, 297 plasma concentration measurements from 31 patients were used to characterize the pharmacokinetics of cefoxitin. A three-compartment mammillary model well-described the pharmacokinetics of cefoxitin. Body weight and creatinine clearance were significant covariates for clearance. The stochastic simulation showed that when compared with the standard method, the TCI method has a significantly higher fraction of time that the free concentration of cefoxitin is maintained above the minimum inhibitory concentration (P < 0.001). Conclusions: TCI has the potential to become a new infusion method for patient-tailored dosing in surgical patients. To administer cefoxitin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.