Midazolam Whole Body Physiologically Based Pharmacokinetic Model

Respiratory Failure Clinical Trial

— MidPBPK  

Official title:

Whole Body Physiologically Based Pharmacokinetic (PBPK) Model to Estimate Cerebral and Systemic Midazolam Concentrations in ICU Patients Under Sedation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01973894
• Other study ID #: 724
• Status: Completed
• Phase: N/A
• First received: August 19, 2012
• Last updated: May 23, 2017
• Start date: January 2013
• Est. completion date: May 2014

Study information

• Verified date: May 2017
• Source: Università degli Studi dell'Insubria
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study investigates what independent variables may influence Midazolam Pharmacokinetics in critically ill patients.

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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coma
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Procedure:
• Blood 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.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi	Varese

Sponsors (2)

Lead Sponsor	Collaborator
Università degli Studi dell'Insubria	University of Milan

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Midazolam concentration in serum and urine	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)	Participants will be followed for the duration of hospital stay, an expected average of 3 weeks
Secondary	Fat mass analysis and its importance in drug distribution.	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.	At enrollment