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the Effect Site Equilibration Time of Propofol is Age Dependant

Phase 4
Completed
Conditions
Healthy
Interventions
Drug: evaluation of propofol effect using BIS
Registration Number
NCT01586013
Lead Sponsor
Universidad del Desarrollo
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
propofol infusionevaluation of propofol effect using BISHealthy 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.
Primary Outcome Measures
NameTimeMethod
pharmacodynamic model for the White propofol pharmacokineticBispectral index

Using a propofol target controlled infusion using de White propofol model, we evaluate a complete curve of depression and recovery of the BIS

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Clinica Alemana

🇨🇱

Santiago de Chile, Chile

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