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Basal level and rate of degradation of the target protein, and apparent rate of inactivation were determined. Impact of down- or up-regulation and rate of synthesis of the target protein on the efficacious doses was also examined. The model showed that, contrary to popular views, high drug clearance could lead to significantly higher doses and that Cmax alone may not be enough for desired extent of inactivation of the target protein even for irreversible inhibitors.

To achieve low and desirable efficacious doses, optimization of drug pharmacokinetics in consult with the target turnover rate, its basal concentration, and drug intrinsic potency is critical.

Objectives: An important aspect of quantitative systems pharmacology QSP model development is the identification of initial parameter values. Published QSP models usually present tables with parameter values including their sources as references. Reliability of the parameter values is never evident, and evaluating each reference individually can be an enormous undertaking for models that have hundreds of parameters.

The aim of this work is to develop a simple, clear, intuitive visualization that aids in evaluating the reliability of parameter sources in a QSP model framework. Methods: Various strategies were investigated for presentation of parameter sources for an internal QSP model under development.

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