Population Pharmacokinetics and Pharmacodynamics of Amiodarone in Children": PK-AMIO
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Maximal Concentration (Cmax) of amiodarone
研究概览
简要总结
PK-AMIO study is a population pharmacokinetic study of Amiodarone in children in order to :
- study the pharmacokinetic parameters (Pop PK) of Amiodarone in children;
- identify covariates explaining the variability of these pharmacokinetic parameters;
- study the relationship between the concentration, the efficacy of treatment and its tolerance to optimize the use of Amiodarone in pediatrics.
Indeed, there is no consensus on the optimal oral dosage in children. Few pharmacokinetic studies have been performed with only a small number of patients per study. Our study will include 70 children aged 0 to 18 years old.
详细描述
The incidence of supraventricular rhythm disorders in children is 1/250 to 1/1000. Amiodarone is used until the age of 1 year to limit the risk of recurrence. Efficiency is around 60% with no predictive factors identified. According to the study by Dallefeld (2018), unexplained inter-individual variability in pharmacokinetic parameters is 200%. Its adverse effects are numerous and affect 10% of patients. The concentration-effect relationship is poorly known. Amiodarone can cause hypotension and bradycardia. Liver and thyroid function should be monitored as well. Amiodarone is metabolised by cytochromes, mainly CYP3A4. Drug interactions and cytochrome variation in the neonatal period may alter its elimination kinetics. Pharmacokinetic studies have been conducted in adults with target concentrations of 0.5 to 2.5 mg/l.
The efficacy of oral amiodarone in children has been shown in studies in 1980; however, there is no consensus on optimal dosage. Despite its widespread use in children, few pharmacokinetic studies have been conducted in a small number of patients at different doses. The population pharmacokinetics and pharmacodynamics of Amiodarone in children, as well as its general and scientific interest, will be studied in this study. The lack of efficacy and the occurrence of adverse events of Amiodarone in children may be related to the large inter-individual pharmacokinetic variability.
Currently, more than 200 children treated with Amiodarone are being followed at Necker-Enfants malades Hospital.
This prospective study will be conducted in three paediatric services of Necker-Enfants malades Hospital in Paris, France.
Patient selection will take place in the 3 paediatric services. The senior physician proposes the study to holders of parental authority whose child receives or will receive the treatment during its follow-up or hospitalization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All children from 0 to 18 years old treated with Amiodarone for any rhythm disorder, and followed to Necker-Enfants maladies hospital.
排除标准
- •Absence of parental and / or child consent
- •Known liver dysfunction
研究组 & 干预措施
Amiodarone dosage
Blood pharmacokinetics samples
干预措施: Blood pharmacokinetic samples (Other)
结局指标
主要结局
Maximal Concentration (Cmax) of amiodarone
时间窗: Hour 0 to Hour 24
Half time of amiodarone
时间窗: Hour 0 to Hour 24
Clearance of amiodarone
时间窗: Hour 0 to Hour 24
Volume of distribution of amiodarone
时间窗: Hour 0 to Hour 24
Area under the plasma concentration versus time curve (AUC) of amiodarone
时间窗: Hour 0 to Hour 24
次要结局
- QT and corrected QT duration(At the beginning of Amiodarone treatment until through study completion, an average of 18 months)
- Blood pressure : (PAS)/(PAD) (mmHg)(At the beginning of Amiodarone treatment until through study completion, an average of 18 months)
- Rhythm disorder(Day 0)
- Altered liver function(At the beginning of Amiodarone treatment until through study completion, an average of 18 months)
- Thyroid Dysfunction(At the beginning of Amiodarone treatment until through study completion, an average of 18 months)