From the Department of Cardiology and Cardiac Surgery, Pediatric Cardiac Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Department of Drug Science and Technology, University of Turin, Turin, Italy.
Pediatr Infect Dis J. 2020 Jul;39(7):609-614. doi: 10.1097/INF.0000000000002635.
Available data about pharmacokinetics (PK) of antimicrobials administered as surgical prophylaxis to children undergoing cardiac surgery with cardiopulmonary bypass (CPB) showed that drug concentrations during CPB may be supra or subtherapeutic. The aim of this study was to determine the population PK and pharmacodynamic target attainment (PTA) of cefoxitin during pediatric CPB surgery.
A prospective interventional study was conducted. Cefoxitin (40 mg/kg, up to max 1000 mg) was administered before skin incision. Blood samples were obtained in the operatory room throughout surgery. Population PK, PTA, and safety of cefoxitin were evaluated in neonates, infants, children <10 and >10 years old.
Forty patients were enrolled. Cefoxitin levels correlated with time from bolus administration (r = -0.6, P = 0.0001) and, after 240 minutes from bolus, drug values below the target (8 mg/L) were shown. Cefoxitin concentrations were best described by a one-compartment model with first order elimination. A significant relationship was identified between body weight, age, body mass index, and serum creatinine on drug clearance and age, body weight, and body mass index on cefoxitin volume of distribution. The PTA for free drug concentration being above the minimum inhibitory concentration of 8 mg/L for at least 240 minutes was >90% in all age groups except in patients >10 years of age (PTA = 62%).
Cefoxitin PK appears to be significantly influenced by CPB with generally reduced drug clearance. The PTA was adequately achieved in the majority of patients except in patients >10 years old or longer surgeries.
现有的关于小儿心脏体外循环（CPB）手术中给予抗菌药物进行手术预防的药代动力学（PK）数据表明，CPB 期间药物浓度可能高于或低于治疗浓度。本研究旨在确定头孢西丁在小儿 CPB 手术中的群体 PK 和药效学目标达标率（PTA）。
进行了一项前瞻性干预研究。在切开皮肤前给予头孢西丁（40mg/kg，最大剂量 1000mg）。在整个手术过程中在手术室采集血样。评估了新生儿、婴儿、<10 岁和>10 岁儿童中头孢西丁的群体 PK、PTA 和安全性。
共纳入 40 例患者。头孢西丁水平与从推注给药开始的时间相关（r = -0.6，P = 0.0001），并且在推注后 240 分钟，显示药物值低于目标值（8mg/L）。头孢西丁浓度最好用单室模型和一级消除来描述。药物清除率与体重、年龄、体重指数和血清肌酐，以及药物分布容积与年龄、体重和体重指数之间存在显著关系。游离药物浓度超过最小抑菌浓度 8mg/L 至少 240 分钟的 PTA 在所有年龄组中均>90%，除>10 岁的患者外（PTA = 62%）。
CPB 显著影响头孢西丁 PK，通常导致药物清除率降低。除了>10 岁或手术时间较长的患者外，大多数患者均能达到足够的 PTA。
