Individual and population pharmacokinetic compartment analysis: a graphic procedure for quantification of predictive performance

Abstract

Objectives:

Pharmacokinetic studies are important for optimizing of drug dosing, but requires proper validation of the used pharmacokinetic procedures. However, simple and reliable statistical methods suitable for evaluation of the predictive performance of pharmacokinetic analysis are essentially lacking. The aim of the present study was to construct and evaluate a graphic procedure for quantification of predictive performance of individual and population pharmacokinetic compartment analysis.

Methods:

Original data from previously published pharmacokinetic compartment analyses after intravenous, oral, and epidural administration, and digitized data, obtained from published scatter plots of observed vs predicted drug concentrations from population pharmacokinetic studies using the NPEM algorithm and NONMEM computer program and Bayesian forecasting procedures, were used for estimating the predictive performance according to the proposed graphical method and by the method of Sheiner and Beal.

Results:

The graphical plot proposed in the present paper proved to be a useful tool for evaluation of predictive performance of both individual and population compartment pharmacokinetic analysis.

Conclusion:

The proposed method is simple to use and gives valuable information concerning time- and concentration-dependent inaccuracies that might occur in individual and population pharmacokinetic compartment analysis. Predictive performance can be quantified by the fraction of concentration ratios within arbitrarily specified ranges, e.g. within the range 0.8–1.2.

Key words::

• Pharmacokinetics
• Predictive performance
• Precision
• Accuracy
• Statistics

Transparency

Declaration of funding

The author received no payment in preparation of this manuscript.

Declaration of financial/other relationships

The author declared no conflicts of interest.

Acknowledgments

Professor Hans Ehrsson is gratefully acknowledged for valuable discussions of the manuscript.