Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, Maryland, USA.
Department of Pharmacy Services, University of Maryland Medical Center, Baltimore, Maryland, USA.
Pharmacotherapy. 2021 Feb;41(2):205-211. doi: 10.1002/phar.2502. Epub 2021 Feb 7.
Currently, no dosing information exists for ceftaroline fosamil in patients undergoing continuous renal replacement therapy (CRRT). The objectives of this study are to characterize the pharmacokinetics of ceftaroline in critically ill patients undergoing CRRT modalities and to derive individualized dosing recommendations.
This pharmacokinetic study aimed to enroll critically ill patients receiving ceftaroline fosamil and any CRRT modality from adult intensive care units. Selection of the specific CRRT modality and dosing regimen was based on clinical discretion. Pre-filter, post-filter, and ultrafiltrate samples were obtained before the administration of the fourth dose, after the completion of the infusion, and up to five additional time points post-infusion. Plasma concentrations were measured using a validated ultra-high performance liquid chromatography assay. Individual pharmacokinetic parameters were calculated using non-compartmental analysis.
Four patients were enrolled to investigate the need for dosing adjustments. The average sieving coefficient for ceftaroline was 0.81 ± 0.1, indicating high filter efficiency. The average volume of distribution was 41.8 L (0.48 L/kg) and is within the previously reported range in patients with normal renal function. Non-renal clearance accounted for more than 50% of the total clearance observed in patients. The observed pharmacokinetic profiles suggest that the pharmacodynamic target for 2-log CFU reduction from baseline (%fT >1 mg/L of 50%) was met for each patient. Due to the impact of CRRT and non-renal clearance, dosing recommendations were derived for different ranges of effluent flow rates and adjusted body weights. For a patient with an adjusted body weight of 70 kg and receiving CRRT at an effluent flow rate of 3 L/h, a ceftaroline fosamil dosing regimen of 400 mg every 12 h is proposed.
Ceftaroline is cleared extensively in critically ill patients receiving CRRT and may impact pharmacodynamic target achievement. Dose adjustments should be based on the intensity of the CRRT regimen, patient weight, and the clinical status of the patient.
目前，头孢洛林在接受连续肾脏替代治疗（CRRT）的患者中尚无剂量信息。本研究的目的是描述接受 CRRT 模式的危重症患者中头孢洛林的药代动力学特征，并得出个体化给药建议。
这项药代动力学研究旨在招募接受头孢洛林治疗的危重症患者，这些患者来自成人重症监护病房，接受任何 CRRT 模式。具体 CRRT 模式和剂量方案的选择基于临床判断。在第四剂给药前、输注完成后以及输注后五个额外时间点采集预滤器、后滤器和超滤样本。使用经验证的超高效液相色谱法测量血浆浓度。使用非房室分析计算个体药代动力学参数。
招募了 4 名患者来调查是否需要调整剂量。头孢洛林的平均筛系数为 0.81±0.1，表明滤器效率高。平均分布容积为 41.8 L（0.48 L/kg），在肾功能正常的患者中报告的范围之内。非肾清除率占观察到的总清除率的 50%以上。观察到的药代动力学特征表明，每位患者均达到了从基线降低 2 对数 CFU 的药效学目标（%fT >1 毫克/升的 50%）。由于 CRRT 和非肾清除的影响，针对不同的流出液流速和调整后的体重范围推导出了给药建议。对于调整后体重为 70 公斤且接受 3 L/h 流出液流速的 CRRT 的患者，建议头孢洛林剂量为 400 毫克，每 12 小时给药一次。
在接受 CRRT 的危重症患者中，头孢洛林被广泛清除，可能影响药效学目标的实现。剂量调整应基于 CRRT 方案的强度、患者体重和患者的临床状况。
