Esteban-Cartelle Beatriz, Anaya Brayan J, Pérez Menéndez-Conde Covadonga, Vicente-Oliveros Noelia, Serrano Dolores R, Álvarez-Díaz Ana, Fortún-Abete Jesús, Martín-Dávila Pilar
Department of Pharmaceutics and Food Technology, School of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal, 28040, Madrid, Spain.
Pharmacy Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
Infect Dis Ther. 2025 Jul 2. doi: 10.1007/s40121-025-01174-7.
Ceftobiprole medocaril is a new fifth-generation cephalosporin commercially available as a prodrug. Since it is newly introduced in therapy, there is limited data on its physicochemical stability for outpatient parenteral antimicrobial therapy (OPAT). This work aimed to demonstrate the suitability of ceftobiprole medocaril in OPAT, determining the physicochemical stability within portable elastomeric infusion devices (Accufuser C0100L 10 mL/h 300 mL).
Physicochemical stability was evaluated in 6.25 mg/mL solutions in sodium chloride 0.9% and dextrose 5% at three temperatures (2-8 °C, 25 °C, and 32 °C) using a previously validated liquid chromatography triple quadrupole mass spectrometry (LC-QQQ-MS) method. Drug adsorption onto device walls was also determined at the end of the study.
Ceftobiprole medocaril remained above 95% of the initial concentration in sodium chloride 0.9% for up to 24 h at both refrigerated (2-8 °C) and ambient conditions (25 °C). Stability was reduced in dextrose 5% solutions. While pH increased slightly over time, it remained within acceptable limits for intravenous administration, and no particle formation was detected. Drug adsorption to the elastomeric device was negligible (< 0.1%).
Ceftobiprole medocaril is suitable for administration in OPAT at 6.25 mg/mL in sodium chloride 0.9% over 24 h at 25 °C using Accufuser portable elastomeric infusion devices. These findings support the development of practical administration protocols for ceftobiprole medocaril in home-based antimicrobial therapy. Ceftobiprole medocaril is a new antibiotic used to treat serious infections. Because it was recently introduced, there is limited information about its stability when used for outpatient parenteral antimicrobial therapy (OPAT), a treatment that allows patients to receive intravenous antibiotics at home using portable elastomeric infusion devices. This study examined how stable ceftobiprole medocaril remains when stored and administered in portable elastomeric infusion devices. The antibiotic was diluted in two commonly used fluids (saline and dextrose) and kept at different temperatures: refrigerated (2-8 °C), room temperature (25 °C), and body temperature (32 °C). Researchers measured how much of the drug remained active over 24 hours and whether it adhered to the inside of the device. The results showed that ceftobiprole medocaril in saline solution (sodium chloride 0.9%) remained stable for 24 hours at room temperature and when refrigerated, keeping over 95% of its original amount. In dextrose, the drug was less stable. The pH changed slightly, but no harmful particles formed, and less than 0.1% of the drug stuck to the infusion device, confirming that the device is suitable for this use. On the basis of these findings, ceftobiprole medocaril can be safely administered in saline solution over 24 hours at room temperature using portable infusion devices. This helps support safe and effective use of the antibiotic in OPAT settings.
头孢比普唑美卡利尔是一种新型的第五代头孢菌素，以前药形式上市。由于它是新引入治疗的药物，关于其在门诊肠外抗菌治疗（OPAT）中的物理化学稳定性的数据有限。这项工作旨在证明头孢比普唑美卡利尔在OPAT中的适用性，确定其在便携式弹性输液装置（Accufuser C0100L，10 mL/h，300 mL）中的物理化学稳定性。
使用先前验证的液相色谱三重四极杆质谱（LC-QQQ-MS）方法，在三种温度（2-8°C、25°C和32°C）下，对0.9%氯化钠溶液和5%葡萄糖溶液中浓度为6.25 mg/mL的溶液进行物理化学稳定性评估。在研究结束时还测定了药物在装置壁上的吸附情况。
在冷藏（2-8°C）和环境条件（25°C）下，头孢比普唑美卡利尔在0.9%氯化钠溶液中初始浓度的95%以上可保持长达24小时。在5%葡萄糖溶液中稳定性降低。虽然pH值随时间略有升高，但仍在静脉给药可接受的范围内，且未检测到颗粒形成。药物在弹性装置上的吸附可忽略不计（<0.1%）。
使用Accufuser便携式弹性输液装置，头孢比普唑美卡利尔在25°C下以6.25 mg/mL的浓度在0.9%氯化钠溶液中用于OPAT给药24小时是合适的。这些发现支持了头孢比普唑美卡利尔在家庭抗菌治疗中实用给药方案的制定。头孢比普唑美卡利尔是一种用于治疗严重感染的新型抗生素。由于它是最近引入的，关于其用于门诊肠外抗菌治疗（OPAT）时的稳定性信息有限，OPAT是一种允许患者在家中使用便携式弹性输液装置接受静脉抗生素治疗的方法。本研究考察了头孢比普唑美卡利尔在便携式弹性输液装置中储存和给药时的稳定性。该抗生素在两种常用液体（盐水和葡萄糖）中稀释，并保持在不同温度下：冷藏（2-8°C）、室温（25°C）和体温（32°C）。研究人员测量了24小时内药物仍保持活性的量以及它是否附着在装置内部。结果表明，盐溶液（0.9%氯化钠）中的头孢比普唑美卡利尔在室温下和冷藏时24小时内保持稳定，保持其原始量的95%以上。在葡萄糖中，药物稳定性较差。pH值略有变化，但未形成有害颗粒，且不到0.1%的药物附着在输液装置上，证实该装置适用于此用途。基于这些发现，头孢比普唑美卡利尔在室温下使用便携式输液装置在盐溶液中24小时内可安全给药。这有助于支持该抗生素在OPAT环境中的安全有效使用。
