Respiratory Failure, Coma
Conditions
Keywords
PBPK, Midazolam, Pharmacokinetics, Critically ill patients
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.
Interventions
PROCEDUREBlood and urine sampling
Blood and urine sampling will follow this schedule: * 24h: blood (3ml) * 48h: blood (3ml) and urine * End of infusion: blood (3ml) * 6h after end of infusion: blood (3ml) and urine. Blood samples will be centrifuged for 10 minutes at 3300rpm, then supernatant will be placed into test tubes and stored at -20°C; urine samples will be freeze at -20°C as well. Then all frozen samples will be analyzed to get Midazolam concentrations.
Sponsors
University of Milan
Università degli Studi dell'Insubria
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Italy
Outcome results
None listed