Author(s): Ludden TM, Beal SL, Sheiner LB
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Abstract In pharmacokinetic data analysis, it is frequently necessary to select the number of exponential terms in a polyexponential expression used to describe the concentration-time relationship. The performance characteristics of several selection criteria, the Akaike Information Criterion (AIC), and the Schwarz Criterion (SC), and the F test (alpha = 0.05), were examined using Monte Carlo simulations. In particular, the ability of these criteria to select the correct model, to select a model allowing estimation of pharmacokinetic parameters with small bias and good precision, and to select a model allowing precise predictions of concentration was evaluated. To some extent interrelationships among these procedures is explainable. Results indicate that the F test tends to choose the simpler model more often than does either the AIC or SC, even when the more complex model is correct. Also, the F test is more sensitive to deficient sampling designs. Clearance estimates are generally very robust to the choice of the wrong model. Other pharmacokinetic parameters are more sensitive to model choice, particularly the apparent elimination rate constant. Prediction of concentrations is generally more precise when the correct model is chosen. The tendency for the F test (alpha = 0.05) to choose the simpler model must be considered relative to the objectives of the study.
This article was published in J Pharmacokinet Biopharm
and referenced in Pharmaceutica Analytica Acta