Midazolam Whole Body Physiologically Based Pharmacokinetic Model
- Conditions
- ComaRespiratory Failure
- Registration Number
- NCT01973894
- Lead Sponsor
- Università degli Studi dell'Insubria
- Brief Summary
This study investigates what independent variables may influence Midazolam Pharmacokinetics in critically ill patients.
- Detailed Description
This study has three specific aims:
1. to create a Midazolam PBPK model based on anthropometric and physiopathological data from enrolled patients;
2. to estimate cerebral and systemic Midazolam concentrations;
3. to assess independent variables about Midazolam pharmacokinetic in critically ill patients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- 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
- Any endocranial lesion, spontaneous or induced
- PaCO2 > 60 mmHg or < 30 mmHg
- PaO2 < 50 mmHg
- Pregnancy
- Anuria
- Any transplantation
- Severe hepatic failure (Child C)
- Life expectancy < 72h
- Ketoconazole and antiretrovirals in therapy
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Midazolam concentration in serum and urine 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)
- Secondary Outcome Measures
Name Time Method Fat mass analysis and its importance in drug distribution. At enrollment At enrollment we will collect data about fat mass in our population. Our goal is to determine how much this variable can modify the distribution of Midazolam in the body. Statistical analysis will performed to found if different body mass values are correlated with different blood concentration of Midazolam at steady level.
Trial Locations
- Locations (1)
Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi🇮🇹Varese, Italy