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 of cefoxitin was dissolved in 50 mL of saline and administered for 10 minutes prior to skin incision. Arterial blood samples were obtained at preset intervals to measure the total and free plasma concentrations of cefoxitin. Population pharmacokinetic analysis was performed using NONMEM software (ICON Development Solutions, Dublin, Ireland). Additionally, 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 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 <.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.
Bibliographical noteFunding Information:
We are deeply grateful to the patients who participated in this study. We hope that this model will be helpful, either directly or indirectly, in patients receiving cefoxitin. We are grateful to Ju-Yeon Moon, PhD and Yeri Park, PhD from the International Scientific Standards, Inc. (Chuncheon-si, Gangwon-do, South Korea) for measuring the plasma concentrations of cefoxitin. We are also grateful to Jeong-Sim Yang, AS (Asan Medical Center, Seoul, South Korea) and Do-Yang Park, AS (Asan Medical Center, Seoul, South Korea) for their efforts as clinical research coordinators. We thank Dr Joon Seo Lim from the Scientific Publications Team at the Asan Medical Center for his editorial assistance in preparing this manuscript. This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: KMDF_PR_20200901_0031, 202011B25-01). This study was supported by a Student Research Grant (20) from the University of Ulsan College of Medicine, Seoul, South Korea.
This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: KMDF_PR_20200901_0031, 202011B25‐01). This study was supported by a Student Research Grant (20) from the University of Ulsan College of Medicine, Seoul, South Korea.
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