Amikacin pharmacokinetics in elderly patients with severe infections,European Journal of Pharmaceutical Sciences

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Amikacin pharmacokinetics in elderly patients with severe infections
European Journal of Pharmaceutical Sciences ( IF 4.3 ) Pub Date : 2022-05-23 , DOI: 10.1016/j.ejps.2022.106219
Susanna E Medellín-Garibay ₁ , Melissa Romano-Aguilar ₁ , Alejandro Parada ₁ , David Suárez ₂ , Silvia Romano-Moreno ₁ , Emilia Barcia ₃ , Miguel Cervero ₂ , Benito García ₂

Affiliation

Objective

The aim of this study was to characterize the population pharmacokinetics of amikacin in elderly patients by means of nonlinear mixed effects modelling and to propose initial dosing schemes to optimize therapy based on PK/PD targets.

Method

A total of 137 elderly patients from 65 to 94 years receiving intravenous amikacin and routine therapeutic drug monitoring at Hospital Universitario Severo Ochoa were included. Concentration–time data and clinical information were retrospectively collected; initial doses of amikacin ranged from 5.7 to 22.5 mg/kg/day and each patient provided between 1 and 10 samples.

Results

Amikacin pharmacokinetics were best described by a two-compartment open model; creatinine clearance (CrCL) was related to drug clearance (2.75 L/h/80 mL/min) and it was augmented 28% when non-steroidal anti-inflammatory drugs were concomitantly administered. Body mass index (BMI) influenced the central volume of distribution (17.4 L/25 kg/m²). Relative absolute prediction error was reduced from 33.2% (base model) to 17.9% (final model) when predictive performance was evaluated with a different group of elderly patients. A nomogram for initial amikacin dosage was developed and evaluated based on stochastic simulations considering final model to achieve PK/PD targets (Cmax/MIC>10 and AUC/MIC>75) and to avoid toxic threshold (Cmin<2.5 mg/L).

Conclusion

Initial dosing approach for amikacin was designed for elderly patients based on nonlinear mixed effects modeling to maximize the probability to attain efficacy and safety targets considering individual BMI and CrCL.

中文翻译：

阿米卡星在老年重症感染患者中的药代动力学

客观的

本研究的目的是通过非线性混合效应模型来表征阿米卡星在老年患者中的群体药代动力学，并提出初始给药方案以优化基于 PK/PD 目标的治疗。

方法

共有 137 名 65 至 94 岁的老年患者在 Severo Ochoa 大学接受静脉注射阿米卡星和常规治疗药物监测。回顾性收集集中时间数据和临床信息；阿米卡星的初始剂量范围为 5.7 至 22.5 mg/kg/天，每位患者提供 1 至 10 个样本。

结果

阿米卡星的药代动力学最好用两室开放模型来描述；肌酐清除率 (CrCL) 与药物清除率 (2.75 L/h/80 mL/min) 相关，当同时使用非甾体抗炎药时，其增加了 28%。体重指数 (BMI) 影响中心分布容积 (17.4 L/25 kg/m ² )。当用不同的老年患者组评估预测性能时，相对绝对预测误差从 33.2%（基本模型）降低到 17.9%（最终模型）。基于随机模拟开发和评估初始阿米卡星剂量的列线图，考虑最终模型以实现 PK/PD 目标（Cmax/MIC>10 和 AUC/MIC>75）并避免毒性阈值（Cmin<2.5 mg/L）。