The expected advantage of administering prophylactic antibiotics using target- concentration controlled infusion: Development of a new pharmacokinetic model of cefazolin

Abstract

The aim of this study was to explore the utility of target-concentration controlled infusion (TCI) as a prophylactic antibiotic administration method based on the results of a population pharmacokinetic model of cefazolin. In patients undergoing elective gastric surgery, 2 g of cefazolin was dissolved in 50 mL of saline and administered for 10 min prior to skin incision. Arterial blood samples were obtained at preset intervals to measure the total and free plasma concentrations of cefazolin. Population pharmacokinetic analysis was performed using non-linear mixed-effects modelling. To evaluate the effectiveness of the TCI method, stochastic simulation was performed based on the model construction results. In total, 360 total and 360 free plasma concentration measurements from 40 patients were used to characterise the pharmacokinetics of cefazolin. The changes in the total concentration of cefazolin over time were well-explained by the three-compartment mammillary model. Fat-free mass and estimated glomerular filtration rate were significant covariates. The probability of target attainment (PTA) to reach the target 100% fraction of time that the free plasma concentration of cefazolin was maintained above its minimal inhibitory concentration (fT > MIC) at MIC of 4 mg/L was also notably higher in the TCI method (90.7%) than in the standard method (17.0%). When cefazolin is administered by the TCI method, patient-tailored antibiotic dosing may be possible. The potential benefits of administering prophylactic antibiotics by the TCI method were observed. Further research is warranted to confirm the effectiveness of the TCI method.