Cefuroxime (CXM) is an antibiotic recommended for surgical site infection prevention in cardiac surgery. However, the dosing regimens commonly used do not sustain therapeutic concentrations throughout surgery. The aim of this study was to conduct a population analysis of CXM pharmacokinetics (PK), and to propose an optimized dosing regimen. Adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) received a 1,500 mg CXM intravenous bolus followed by a 750 mg bolus at CPB priming, then every 2 h thereafter. Model-based PK simulations were used to develop an optimized dosing regimen and evaluate its efficacy in attaining various concentration thresholds, including those recommended in US and European guidelines. In total, 447 CXM measurements were acquired in 50 patients. A two-compartment model best fit the data, with total body weight and creatinine clearance determining interpatient variability in the central and peripheral volumes of distribution, and in elimination clearance, respectively. Using our optimized dosing regimen, different dosing schemes adapted to body weight and renal function were calculated to attain total concentration thresholds ranging from 12 to 96 mg/liter. Our simulations showed that the dosing regimens recommended in US and European guidelines failed to maintain concentrations above 48 mg/liter. Our individualized dosing strategy was capable of ensuring therapeutic CXM concentrations conforming to each target threshold. Our model yielded an optimized CXM dosing regimen adapted to body weight and renal function, and sustaining therapeutic concentrations consistent with each desired threshold. The optimal target concentration and necessary duration of its maintenance in cardiac surgery still remain unclear.

中文翻译：

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体外循环下心脏手术中头孢呋辛给药的药代动力学模型

头孢呋辛（CXM）是一种推荐用于预防心脏手术中手术部位感染的抗生素。但是，常用的给药方案在整个手术过程中不能维持治疗浓度。这项研究的目的是进行CXM药代动力学（PK）的人群分析，并提出一种优化的给药方案。在体外循环（CPB）下接受心脏手术的成年患者在初次启动时接受1,500 mg CXM静脉推注，然后是750 mg推注，此后每2 h接受一次。基于模型的PK模拟用于开发优化的给药方案并评估其在达到各种浓度阈值（包括美国和欧洲指南中建议的浓度阈值）中的功效。总共在50位患者中进行了447次CXM测量。两室模型最适合数据，总体重和肌酐清除率分别决定了患者之间在中心和周围分布的容积以及消除清除率方面的差异。使用我们优化的给药方案，可以计算出适合体重和肾功能的不同给药方案，以达到12至96 mg / L的总浓度阈值。我们的模拟结果表明，美国和欧洲准则中推荐的给药方案未能将浓度维持在48 mg / L以上。我们的个性化给药策略能够确保治疗性CXM浓度符合每个目标阈值。我们的模型产生了适合体重和肾功能的优化CXM给药方案，并维持与每个所需阈值一致的治疗浓度。