the Effect Site Equilibration Time of Propofol is Age Dependant

NCT ID: NCT01586013

Last Updated: 2012-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2011-08-31

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.

Conditions

Healthy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

propofol infusion

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.

Group Type: EXPERIMENTAL

evaluation of propofol effect using BIS

Intervention Type: DRUG

propofol administered in target controlled infusion using the pharmacokinetic model of White

Interventions

evaluation of propofol effect using BIS

propofol administered in target controlled infusion using the pharmacokinetic model of White

Intervention Type: DRUG

Other Intervention Names

evaluation of effect of intravenous di-isopropilfenol

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universidad del Desarrollo

OTHER

Sponsor Role: lead

Responsible Party

Pablo Sepulveda

Dr Med

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pablo O Sepulveda, Dr

Role: PRINCIPAL_INVESTIGATOR

Clinica Alemana Universidad del Desarrollo

Locations

Clinica Alemana

Santiago, , Chile

Countries

Chile

References

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. doi: 10.2165/00003088-200847020-00005.

Reference Type: BACKGROUND

PMID: 18193918 (View on PubMed)

Other Identifiers

PSepulveda_ke0age

Identifier Type: -

Identifier Source: org_study_id