the Effect Site Equilibration Time of Propofol is Age Dependant

Healthy Clinical Trial

— ke0agedep  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01586013
• Other study ID #: PSepulveda_ke0age
• Status: Completed
• Phase: Phase 4
• First received: April 19, 2012
• Last updated: April 25, 2012
• Start date: October 2010
• Est. completion date: August 2011

Study information

• Verified date: April 2012
• Source: Universidad del Desarrollo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Chile: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• evaluation of propofol effect using BIS
propofol administered in target controlled infusion using the pharmacokinetic model of White

Locations

Country	Name	City	State
Chile	Clinica Alemana	Santiago de Chile

Sponsors (1)

Lead Sponsor	Collaborator
Universidad del Desarrollo

Country where clinical trial is conducted

Chile, 

References & Publications (1)

White M, Kenny GN, Schraag S. Use of target controlled infusion to derive age and gender covariates for propofol clearance. Clin Pharmacokinet. 2008;47(2):119-27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes