重症患者头孢他啶的负荷剂量需要增加:利用药代动力学模型评估推荐负荷剂量的回顾性研究

Manon Launay, Edouard Ollier, Benjamin Kably, Félicien Le Louedec, Guillaume Thiery, Julien Lanoiselée, Sophie Perinel-Ragey
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引用次数: 0

摘要

为了快速达到头孢他啶的目标浓度,建议在持续输注前使用 2 克负荷剂量(LD),但鉴于重症患者独特的药代动力学,该剂量是否足够还需研究。这项研究纳入了来自法国圣埃蒂安和巴黎六家重症监护室的患者,他们接受了头孢他啶持续输注,并进行了血浆浓度测量。研究人员使用 MONOLIX 和 R 开发了一个药代动力学(PK)模型,并查阅了有关 ICU 患者 PK 模型的文献。模拟计算了达到 60 mg/L 目标浓度所需的 LD,并评估了各种治疗方案的头孢他啶暴露量。在 86 位患者的 223 份样本中,头孢他啶的 PK 用单室模型进行了最佳描述,肾小球滤过率可解释清除率的变化。典型的清除率和分布容积分别为 4.45 升/小时和 88 升。模拟结果表明,80% 的患者需要大于 2 克的 LD 才能达到 60 毫克/升,中位 LD 为 4.9 克。我们的模型显示,4 克 LD 后再输注 6 克/天,可在 1 小时内达到有效浓度,而 2 克 LD 会导致达到目标稳态的时间延迟 18 小时。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Loading Dose of Ceftazidime Needs to Be Increased in Critically Ill Patients: A Retrospective Study to Evaluate Recommended Loading Dose with Pharmacokinetic Modelling
To rapidly achieve ceftazidime target concentrations, a 2 g loading dose (LD) is recommended before continuous infusion, but its adequacy in critically ill patients, given their unique pharmacokinetics, needs investigation. This study included patients from six ICUs in Saint-Etienne and Paris, France, who received continuous ceftazidime infusion with plasma concentration measurements. Using MONOLIX and R, a pharmacokinetic (PK) model was developed, and the literature on ICU patient PK models was reviewed. Simulations calculated the LD needed to reach a 60 mg/L target concentration and assessed ceftazidime exposure for various regimens. Among 86 patients with 223 samples, ceftazidime PK was best described by a one-compartment model with glomerular filtration rate explaining clearance variability. Typical clearance and volume of distribution were 4.45 L/h and 88 L, respectively. The literature median volume of distribution was 37.2 L. Simulations indicated that an LD higher than 2 g was needed to achieve 60 mg/L in 80% of patients, with a median LD of 4.9 g. Our model showed a 4 g LD followed by 6 g/day infusion reached effective concentrations within 1 h, while a 2 g LD caused an 18 h delay in achieving target steady state.
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