Population Pharmacokinetic Model for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass: Model-Based Evaluation of Standard Dosing Regimens [PublishAheadOfPrint]

The purpose of this study was to investigate the population PK of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples were analyzed from 78 patients. The PK for cefuroxime was best described by a two-compartment model with between-subject variability on clearance, volume of the central compartment, and volume of the peripheral compartment. Clearance of cefuroxime was related to creatinine clearance (CL_CR). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of 65% fT_>MIC for an MIC of 8 mg/L in patients with CL_CR of 30, 60, 90 ml/min, whereas this dosing regimens failed to achieve the PK-PD target in patients with CL_CR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CL_CR values are required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CLCR (≤30 ml/min).

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