2007 - KÝbenhavn - Denmark

PAGE 2007: Methodology- Model evaluation
Douglas J. Eleveld

Is the expected performance of a target-controlled-infusion system influenced by the population analysis method

D J Eleveld (1), J K G Wietasch (2), J H Proost (1), S Guzy(3), A Hoeft (4)

(1) Research Group for Experimental Anesthesiology and Clinical Pharmacology , Department of Anesthesiology, University Medical Center Groningen, The Netherlands; (2) Department of Anesthesiology, University Medical Center Groningen, The Netherlands; (3) POP-PHARM; XOMA; (4) Department of Anesthesiology and Intensive Care medicine, University of Bonn, Germany;

Objectives: Target controlled infusion (TCI) uses a pharmacokinetic (PK) model to estimate drug infusion rates required to rapidly achieve a desired drug concentration. 

Objectives: Target controlled infusion (TCI) uses a pharmacokinetic (PK) model to estimate drug infusion rates required to rapidly achieve a desired drug concentration.  Currently available TCI systems allow the user to determine the PK model used for drug concentration predictions and the model chosen is often the typical value of a population analysis.  A number of population analysis methods are available and, given the same data, each method results in different estimated population typical values.  Our objective was to determine whether NONMEM [1], MCPEM[2] or ITSB[3] population analysis methods provided a PK model best suited for use in a TCI system.

Methods: We measured propofol concentrations in 56 patients undergoing cardiac surgery where sufentanil was used as an analgesic and estimated 3-compartment population PK models using NONMEM, MCPEM and ITSB methods.  We estimated the performance of a TCI system based on population typical values in simulation with Monte-Carlo methods with the Median (Absolute) Performance Error (MdPE, MdAPE).  We also tested previously published propofol PK parameter sets.

Results: Small differences in TCI system MdPE values were found between the methods but the MdAPE values were very similar.  On average, population typical values from NONMEM, MCPEM and ITSB analysis methods provided essentially equal TCI system performance error.

Conclusions: We conclude that population typical values from NONMEM, MCPEM or ITSB are equally suited for use in TCI systems.

References:
[1] Sheiner LB, Ludden TM. Population pharmacokinetics/dynamics. Ann. Rev. Pharmacol. Toxicol 1992;  32:185-209
[2]Bauer RJ, Guzy S. Monte Carlo Parametric Expectation Maximization (MCPEM) Method for Analyzing Population Pharmacokinetic/ Pharmacodynamic (PK/PD) Data. In: D.Z. D'Argenio, ed. Advanced Methods of Pharmacokinetic and Pharmacodynamics Systems Analysis, Vol.3. Boston: Kluwer Academic Publishers (2004),pp 135-163
[3]Proost JH, Eleveld DJ. Performance of an Iterative Two-Stage Bayesian Technique for Population Pharmacokinetic Analysis of Rich Data Sets. Pharmaceutical Research 2006; 23: 2748-59




Reference: PAGE 16 (2007) Abstr 1077 [www.page-meeting.org/?abstract=1077]
Poster: Methodology- Model evaluation
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