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An evaluation of using population pharmacokinetic models to estimate pharmacodynamic parameters for propofol and bispectral index in children

MARC COPPENS UGent, Douglas J Eleveld, Johannes H Proost, Luc Marks UGent, Jan Van Bocxlaer UGent, Hugo Vereecke, Anthony R Absalom and Michel Struys UGent (2011) ANESTHESIOLOGY. 115(1). p.83-93
abstract
Background: To study propofol pharmacodynamics in a clinical setting a pharmacokinetic model must be used to predict drug plasma concentrations. Some investigators use a population pharmacokinetic model from existing literature and minimize the pharmacodynamic objective function. The purpose of the study was to determine whether this method selects the best-performing pharmacokinetic model in a set and provides accurate estimates of pharmacodynamic parameters in models for bispectral index in children after propofol administration. Methods: Twenty-eight children classified as American Society of Anesthesiologists physical status 1 who were given general anesthesia for dental treatment were studied. Anesthesia was given using target-controlled infusion of propofol based on the Kataria model. Propofol target plasma concentration was 7 mu g/ml for 15 min, followed by 1 mu g/ml for 15 min or until signs of awakening, followed by 5 mu g/ml for 15 min. Venous blood samples were taken 1, 2, 5, 10, and 15 min after each change in target. A classic pharmacokinetic-pharmacodynamic model was estimated, and the methodology of other studies was duplicated using pharmacokinetic models from the literature and (re-)estimating the pharmacodynamic models. Results: There is no clear relationship between pharmacokinetic precision and the pharmacodynamic objective function. Low pharmacodynamic objective function values are not associated with accurate estimation of the pharmacodynamic parameters when the pharmacokinetic model is taken from other sources. Conclusion: Minimization of the pharmacodynamic objective function does not select the most accurate pharmacokinetic model. Using population pharmacokinetic models from the literature instead of the 'true' pharmacokinetic model can lead to better predictions of bispectral index while incorrectly estimating the pharmacodynamic parameters.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CONTROLLED INFUSION, TIME, PERFORMANCE, SEDATION, BOLUS, ANESTHESIA, SURGERY, VS. SEQUENTIAL-ANALYSIS
journal title
ANESTHESIOLOGY
Anesthesiology
volume
115
issue
1
pages
83 - 93
Web of Science type
Article
Web of Science id
000291925400014
JCR category
ANESTHESIOLOGY
JCR impact factor
5.359 (2011)
JCR rank
2/28 (2011)
JCR quartile
1 (2011)
ISSN
0003-3022
DOI
10.1097/ALN.0b013e31821a8d80
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1900252
handle
http://hdl.handle.net/1854/LU-1900252
date created
2011-09-13 09:55:55
date last changed
2011-09-13 11:31:54
@article{1900252,
  abstract     = {Background: To study propofol pharmacodynamics in a clinical setting a pharmacokinetic model must be used to predict drug plasma concentrations. Some investigators use a population pharmacokinetic model from existing literature and minimize the pharmacodynamic objective function. The purpose of the study was to determine whether this method selects the best-performing pharmacokinetic model in a set and provides accurate estimates of pharmacodynamic parameters in models for bispectral index in children after propofol administration. 
Methods: Twenty-eight children classified as American Society of Anesthesiologists physical status 1 who were given general anesthesia for dental treatment were studied. Anesthesia was given using target-controlled infusion of propofol based on the Kataria model. Propofol target plasma concentration was 7 mu g/ml for 15 min, followed by 1 mu g/ml for 15 min or until signs of awakening, followed by 5 mu g/ml for 15 min. Venous blood samples were taken 1, 2, 5, 10, and 15 min after each change in target. A classic pharmacokinetic-pharmacodynamic model was estimated, and the methodology of other studies was duplicated using pharmacokinetic models from the literature and (re-)estimating the pharmacodynamic models. 
Results: There is no clear relationship between pharmacokinetic precision and the pharmacodynamic objective function. Low pharmacodynamic objective function values are not associated with accurate estimation of the pharmacodynamic parameters when the pharmacokinetic model is taken from other sources. 
Conclusion: Minimization of the pharmacodynamic objective function does not select the most accurate pharmacokinetic model. Using population pharmacokinetic models from the literature instead of the 'true' pharmacokinetic model can lead to better predictions of bispectral index while incorrectly estimating the pharmacodynamic parameters.},
  author       = {COPPENS, MARC and Eleveld, Douglas J and Proost, Johannes H and Marks, Luc and Van Bocxlaer, Jan and Vereecke, Hugo and Absalom, Anthony R and Struys, Michel},
  issn         = {0003-3022},
  journal      = {ANESTHESIOLOGY},
  keyword      = {CONTROLLED INFUSION,TIME,PERFORMANCE,SEDATION,BOLUS,ANESTHESIA,SURGERY,VS. SEQUENTIAL-ANALYSIS},
  language     = {eng},
  number       = {1},
  pages        = {83--93},
  title        = {An evaluation of using population pharmacokinetic models to estimate pharmacodynamic parameters for propofol and bispectral index in children},
  url          = {http://dx.doi.org/10.1097/ALN.0b013e31821a8d80},
  volume       = {115},
  year         = {2011},
}

Chicago
Coppens, Marc, Douglas J Eleveld, Johannes H Proost, Luc Marks, Jan Van Bocxlaer, Hugo Vereecke, Anthony R Absalom, and Michel Struys. 2011. “An Evaluation of Using Population Pharmacokinetic Models to Estimate Pharmacodynamic Parameters for Propofol and Bispectral Index in Children.” Anesthesiology 115 (1): 83–93.
APA
Coppens, Marc, Eleveld, D. J., Proost, J. H., Marks, L., Van Bocxlaer, J., Vereecke, H., Absalom, A. R., et al. (2011). An evaluation of using population pharmacokinetic models to estimate pharmacodynamic parameters for propofol and bispectral index in children. ANESTHESIOLOGY, 115(1), 83–93.
Vancouver
1.
Coppens M, Eleveld DJ, Proost JH, Marks L, Van Bocxlaer J, Vereecke H, et al. An evaluation of using population pharmacokinetic models to estimate pharmacodynamic parameters for propofol and bispectral index in children. ANESTHESIOLOGY. 2011;115(1):83–93.
MLA
Coppens, Marc, Douglas J Eleveld, Johannes H Proost, et al. “An Evaluation of Using Population Pharmacokinetic Models to Estimate Pharmacodynamic Parameters for Propofol and Bispectral Index in Children.” ANESTHESIOLOGY 115.1 (2011): 83–93. Print.