title: Adjustment of endogenous concentrations in pharmacokinetic modeling.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Baxter Innovations GmbH, Vienna, Austria, alexander_bauer@baxter.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bauer
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Wolfsegger
mesh_terms: D019540:Area Under Curve; D003198:Computer Simulation; D006207:Half-Life; D006801:Humans; D008954:Models, Biological; D009010:Monte Carlo Method; D010599:Pharmacokinetics