European Journal of Clinical Pharmacology

, Volume 70, Issue 12, pp 1465–1470 | Cite as

Adjustment of endogenous concentrations in pharmacokinetic modeling

  • Alexander BauerEmail author
  • Martin J. Wolfsegger
Pharmacokinetics and Disposition



Estimating pharmacokinetic parameters in the presence of an endogenous concentration is not straightforward as cross-reactivity in the analytical methodology prevents differentiation between endogenous and dose-related exogenous concentrations. This article proposes a novel intuitive modeling approach which adequately adjusts for the endogenous concentration.


Monte Carlo simulations were carried out based on a two-compartment population pharmacokinetic (PK) model fitted to real data following intravenous administration. A constant and a proportional error model were assumed. The performance of the novel model and the method of straightforward subtraction of the observed baseline concentration from post-dose concentrations were compared in terms of terminal half-life, area under the curve from 0 to infinity, and mean residence time.


Mean bias in PK parameters was up to 4.5 times better with the novel model assuming a constant error model and up to 6.5 times better assuming a proportional error model.


The simulation study indicates that this novel modeling approach results in less biased and more accurate PK estimates than straightforward subtraction of the observed baseline concentration and overcomes the limitations of previously published approaches.


Endogenous concentration Intrinsic concentration Baseline adjustment Pre-dose concentration Pharmacokinetics 



We gratefully acknowledge the editorial expertise of Karima Benamara and the helpful comments from Werner Engl.

Authors contribution

The authors made equal contributions to the development of this manuscript.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Baxter Innovations GmbHViennaAustria

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