the Effect Site Equilibration Time of Propofol is Age Dependant (ke0agedep)

Universidad del Desarrollo

Status and phase: Completed; Phase 4

Conditions: Healthy

Treatments: Drug: evaluation of propofol effect using BIS

Study type: Interventional

Funder types: Other

Identifiers

NCT01586013

PSepulveda_ke0age

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Health Services Research

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

propofol infusion

Experimental group

Description:

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.

Treatment:

Drug: evaluation of propofol effect using BIS