Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Department of Anesthesia and Perioperative Medicine, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa.
CPT Pharmacometrics Syst Pharmacol. 2024 Sep;13(9):1595-1605. doi: 10.1002/psp4.13196. Epub 2024 Jul 4.
Cefazolin is an antibiotic used to prevent surgical site infections. During cardiac surgery with cardiopulmonary bypass (CPB), its efficacy target could be underachieved. We aimed to develop a population pharmacokinetic model for cefazolin in children and optimize the prophylactic dosing regimen. Children under 25 kg undergoing cardiac surgery with CPB and receiving cefazolin at standard doses (50 mg/kg IV every 4-6 h) were included in this analysis. A population pharmacokinetic model and Monte Carlo simulations were used to evaluate the probability of target attainment (PTA) for efficacy and toxicity with the standard regimen and an alternative regimen of continuous infusion, where loading and maintenance doses were calculated from model-derived individual parameters. Twenty-two patients were included, with median (range) age, body weight, and eGFR of 19.5 (1-94) months, 8.7 (2-21) kg, and 116 (48-159) mL/min, respectively. Six patients received an additional dose in the CPB circuit. A two-compartment disposition model with an additional compartment for the CPB was developed, including weight-based allometric scaling and eGFR. For a 10 kg patient with eGFR of 120 mL/min/1.73 m, clearance was estimated as 0.856 L/h. Simulations indicated that the standard dosing regimen fell short of achieving the efficacy target >40% of the time within a dosing duration and in patients with good renal function, PTA ranged from <20% to 70% for the smallest to the largest patients, respectively, at high MICs. In contrast, the alternative regimen consistently maintained target concentrations throughout the procedure for all patients while using a lower overall dose.
头孢唑林是一种用于预防手术部位感染的抗生素。在体外循环（CPB）心脏手术中，其疗效目标可能无法实现。我们旨在为儿童开发头孢唑林的群体药代动力学模型，并优化预防剂量方案。本分析纳入了接受 CPB 心脏手术且标准剂量（50mg/kg IV 每 4-6 小时一次）接受头孢唑林的<25kg 儿童。使用群体药代动力学模型和蒙特卡罗模拟来评估标准方案和连续输注替代方案的疗效和毒性靶达标概率（PTA），其中负荷剂量和维持剂量是根据模型衍生的个体参数计算得出的。共纳入 22 例患者，中位（范围）年龄、体重和 eGFR 分别为 19.5（1-94）个月、8.7（2-21）kg 和 116（48-159）mL/min。6 例患者在 CPB 回路中接受了额外的剂量。建立了一个包含 CPB 附加隔室的两室处置模型，包括基于体重的比例缩放和 eGFR。对于 eGFR 为 120mL/min/1.73m 的 10kg 患者，清除率估计为 0.856L/h。模拟表明，在一个给药时间内，标准给药方案未能达到>40%的疗效目标，在肾功能良好的患者中，从小到最大的患者，PTA 分别为<20%至 70%，MIC 较高。相比之下，替代方案在所有患者中在整个手术过程中始终维持靶浓度，而总剂量较低。
