Whole Body Physiologically Based Pharmacokinetic (PBPK) Model to Estimate Cerebral and Systemic Midazolam Concentrations in ICU Patients Under Sedation.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Midazolam concentration in serum and urine
研究概览
简要总结
This study investigates what independent variables may influence Midazolam Pharmacokinetics in critically ill patients.
详细描述
This study has three specific aims:
- to create a Midazolam PBPK model based on anthropometric and physiopathological data from enrolled patients;
- to estimate cerebral and systemic Midazolam concentrations;
- to assess independent variables about Midazolam pharmacokinetic in critically ill patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ICU admittance
- •Caucasian
- •Clinical indication of least 72h of continuous sedation with Midazolam
- •MAP between 60 - 150 mmHg, even if obtained with amine support
- •informed consent obtained
排除标准
- •Any endocranial lesion, spontaneous or induced
- •PaCO2 > 60 mmHg or < 30 mmHg
- •PaO2 < 50 mmHg
- •Pregnancy
- •Any transplantation
- •Severe hepatic failure (Child C)
- •Life expectancy < 72h
- •Ketoconazole and antiretrovirals in therapy
结局指标
主要结局
Midazolam concentration in serum and urine
时间窗: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks
We will calculate Midazolam AUC in serum and urine using blood and urine samples. With this data we will evaluate the elimination constants and create a Physiologically Based Pharmacokinetic Model for Midazolam simulating the drug concentration profile in brain and fat tissue. The blood and urine samples timing is: * 1 blood sample will be gathered after 24h at the beginning of continuous intravenous infusion of Midazolam * 1 blood sample and 1 urine sample will be gathered after 48h at the beginning of continuous intravenous infusion of Midazolam * 1 blood sample will be gathered at the end of continuous intravenous infusion of Midazolam (the duration of infusion is different for each patient according with clinical case) * 1 blood sample and 1 urine sample will be gathered after 6h at the end of continuous intravenous infusion of Midazolam (the duration of infusion is different for each patient according with clinical case)
次要结局
- Fat mass analysis and its importance in drug distribution.(At enrollment)
研究者
Paolo Severgnini
Prof.
Università degli Studi dell'Insubria