如何在接受CKRT的儿科患者中使用meropenem? 对重症儿童的综合美罗胺药理动力学模型
Laura Butragueño-Laiseca1,2,3,4, Iñaki F Troconiz5,6, Santiago Grau7
1Pediatric Intensive Care Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Antimicrobial agents and chemotherapy
|April 24, 2024
概括
标准的美罗胺剂量对于重症儿童来说通常是不够的,有毒性或次治疗水平的风险. 建议持续或延长输液,特别是在患有脏问题的患者中,以获得最佳的美罗 (一种宽谱抗生素) 剂量.
科学领域:
- 药理动力学和药理动力学
- 儿科重症监护医学 儿科重症监护医学
- 传染性疾病 传染性疾病
背景情况:
- 标准的美罗胺剂量方案可能无法在重症儿童中达到治疗性的全身度.
- 儿科重症监护室 (ICU) 患者,特别是急性损伤 (AKI) 患者的亚治疗水平或毒性是令人担忧的.
- 优化美罗胺剂量对于在弱势儿科群体中有效治疗严重感染至关重要.
研究的目的:
- 在重症儿童中描述美罗的药理动力学特性.
- 评估通过各种美罗胺剂量策略实现目标药理动力学/药理动力学 (PK/PD) 终点 (例如,FT>MIC) 的概率.
- 为儿童ICU患者提供基于证据的推,以个性化治疗儿科ICU患者,包括接受连续脏替代疗法 (CKRT) 的儿科ICU患者.
主要方法:
- 种群药动力学 (Pop-PK) 分析整合了多种不同的美罗胺度数据 (血,过器,尿液).
- 蒙特卡洛模拟用于估计不同间歇和连续输液方案的目标实现概率 (PTA).
- 包括16名重症儿童,其中7名接受CKRT,以评估特定亚群的剂量.
主要成果:
- 没有CKRT的儿童中,只有33%的儿童在标准剂量下达到2 mg/L的最低抑制度 (MIC) 以上90%的目标时间.
- 在没有CKRT的患者<30 kg的情况下,模拟表明持续输注 (60-120 mg/kg/24h) 是必要的.
- 对于接受CKRT的患者来说,长时间输注 (40mg/kg每8小时或3-4小时输注一次) 对于那些>10公斤的患者来说是足够的,而对于<10公斤的患者则需要持续输注. 剂量为患者>30公斤需要60毫克/公斤/24小时连续输注.
结论:
- 目前的美罗胺剂量在重症儿童中经常不足,需要调整剂量.
- 延长或连续的美罗胺输液优于标准的间歇剂量,用于在这个人群中实现治疗目标.
- 一种种群的药理动力学模型支持针对重症儿童,有或没有CKRT的个性化meropenem剂量策略,以优化疗效和最大限度地降低毒性.
相关概念视频
Renal Failure: Dose Adjustments
88
In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
88
One-Compartment Open Model: Urinary Excretion Data and Determination of k
173
The one-compartment open model leverages urinary excretion data to estimate renal clearance, which gauges the kidney's capacity to expel a drug. This method offers several benefits, including directly measuring drug elimination and assessing the kidney's contribution to overall drug clearance. However, this approach has limitations. It assumes sole renal excretion of the drug, which is not true for all drugs. Accurate urinary excretion and plasma drug concentration measurement can also...
173
One-Compartment Model: IV Infusion
194
Intravenous (IV) infusion is often utilized when continuous and controlled drug delivery is necessary, such as during surgery or in the treatment of chronic diseases. This method offers numerous advantages, including immediate drug action, precise control over dosage, and bypassing the first-pass metabolism.
The one-compartment model for IV infusion uses mathematical equations to describe the rate of change in drug quantity in the body. At steady-state or infusion equilibrium, the drug input...
The one-compartment model for IV infusion uses mathematical equations to describe the rate of change in drug quantity in the body. At steady-state or infusion equilibrium, the drug input...
194
Pharmacokinetic Models: Overview
667
Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
667
Factors Affecting Renal Clearance: Renal Impairment
91
Renal dysfunction significantly impairs the renal clearance of drugs, leading to potential complications in drug therapy. Renal failure, which can be caused by various factors, poses a significant challenge in the elimination of drugs from the body.
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
91
Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
60
Noncompartmental analyses offer an alternative method for describing drug pharmacokinetics without relying on a specific compartmental model. In this approach, the drug's pharmacokinetics are assumed to be linear, with the terminal phase log-linear. This assumption allows for simplified analysis and interpretation of the drug's behavior in the body.
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
60


