Performance of an iterative two-stage bayesian technique for population pharmacokinetic analysis of rich data sets.
OBJECTIVE
To test the suitability of an Iterative Two-Stage Bayesian (ITSB) technique for population pharmacokinetic analysis of rich data sets, and to compare ITSB with Standard Two-Stage (STS) analysis and nonlinear Mixed Effect Modeling (MEM).


METHODS
Data from a clinical study with rapacuronium and data generated by Monte Carlo simulation were analyzed by an ITSB technique described in literature, with some modifications, by STS, and by MEM (using NONMEM). The results were evaluated by comparing the mean error (accuracy) and root mean squared error (precision) of the estimated parameter values, their interindividual standard deviation, correlation coefficients, and residual standard deviation. In addition, the influence of initial estimates, number of subjects, number of measurements, and level of residual error on the performance of ITSB were investigated.


RESULTS
ITSB yielded best results, and provided precise and virtually unbiased estimates of the population parameter means, interindividual variability, and residual standard deviation. The accuracy and precision of STS was poor, whereas ITSB performed better than MEM.


CONCLUSIONS
ITSB is a suitable technique for population pharmacokinetic analysis of rich data sets, and in the presented data set it is superior to STS and MEM.
Proost
Johannes H
JH
Research Group for Experimental Anesthesiology and Clinical Pharmacology, Department of Anesthesiology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. j.h.proost@rug.nl
Eleveld
Douglas J
DJ
D000465:Algorithms; D001499:Bayes Theorem; D015982:Bias; D019992:Databases as Topic; D006801:Humans; D015233:Models, Statistical; D009010:Monte Carlo Method; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics; D017711:Nonlinear Dynamics; D010599:Pharmacokinetics; D012107:Research Design; D018401:Sample Size; D012984:Software; D014673:Vecuronium Bromide / Q000031:analogs & derivatives / Q000493:pharmacokinetics
D003473:Neuromuscular Nondepolarizing Agents; D014673:Vecuronium Bromide; C082938:rapacuronium