the Effect Site Equilibration Time of Propofol is Age Dependant

Study Overview
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Brief Summary
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This study obtains an effect site model for White (Modified Marsh) pharmacokinetic propofol model. The plasma effect-site rate constant (ke0) obtained is affected by age.

Detailed Description
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In the Target Controlled Infusion pumps the first order plasma-effect-site steady-state rate constant (ke0) links the pharmacokinetics (PK) and pharmacodynamics (PD) for a given drug and it is used to predict the course of the effect and to calculate a theoretical drug concentration at the effect site. The PK model for propofol recently published by White et al. (derived from the Marsh model used by the Diprifusor®) include covariate as age and gender to describe the pharmacokinetics but does not incorporate a ke0. Methods: 45 healthy adult patients will be scheduled for elective surgery with standard monitoring and BIS XP (Aspect) will received a White PK model-driven plasma target controlled infusion of propofol ( 12 ugml-1 or 10 ugml-1 over 65 years) to be reached in 4 min. After reaching the target, the infusion will be stopped obtaining a complete effect curve upon patient awakening. Calculated plasma concentration and EEG data were stored every one second. Loss (LOC) and recovery (ROC) of consciousness were assessed and recorded. The dynamic relationship between propofol Ce and its effect as measured by BIS will be modeled with an inhibitory Emax model using a population PK/PD approach with NONMEM V. the Study take around 12 min.

Official Title
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Importance of Age as Covariable in the Requirements to Determine the Drug Plasma -Site Effect Equilibration Time for TCI Propofol Pharmacokinetic Models

Conditions
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Healthy

Intervention / Treatment
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* Drug: evaluation of propofol effect using BIS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA 1-2 Exclusion Criteria: less than 70% or more than 130% ideal body mass index, neurologic disorders, pregnancy, psychoactive medication intake during last 48 hours

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: propofol infusion<br>Healthy adults scheduled for elective surgery will receive a computer controlled infusion until obtain the loss of counsiousness (BIS <50). After stoping the infusion we observe the emergency of anesthesia and the correspondant BIS curve. Using the complete loss and recovery curve of BIS we can describe the course of the effect of the drug. Venous sample will be taken during the study to evaluate the pharmacokinetic performance of the model. | Drug: evaluation of propofol effect using BIS<br>* propofol administered in target controlled infusion using the pharmacokinetic model of White<br>* Other names: evaluation of effect of intravenous di-isopropilfenol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacodynamic model for the White propofol pharmacokinetic | Using a propofol target controlled infusion using de White propofol model, we evaluate a complete curve of depression and recovery of the BIS | Bispectral index | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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propofol, pharmacodynamic, age, ke0