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An Extended Model Including Target Turnover, Ligand–Target Complex Kinetics, and Binding Properties to Describe Drug–Receptor Interactions

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Computational Methods for Estimating the Kinetic Parameters of Biological Systems

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2385))

Abstract

Since the beginning of this century, target-mediated drug disposition has become a central concept in modeling drug action in drug development. It combines a range of processes, such as turnover, protein binding, internalization, and non-specific elimination, and often serves as a nucleus of more complex pharmacokinetic models. It is simple enough to comprehend but complex enough to be able to describe a wide range of phenomena and data sets. However, the complexity comes at a price: many parameters. In this chapter, we present an overview of the temporal development of the compounds involved after different types of drug doses and offer convenient handles for dissecting data sets in a sophisticated manner in order to estimate the values of these parameters, such as rate constants and pertinent concentrations.

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Notes

  1. 1.

    Here F

    L means F approaches L from below and G

    L means G approaches L from above.

  2. 2.

    We write f(x) ∼ A ⋅ g(x) as x → 0 (∞) if: f(x)∕g(x) → A as x → 0 (∞).

  3. 3.

    time-Averaged Free Target concentration to Initial target concentration Ratio.

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Acknowledgement

It is a great pleasure to thank Johan Gabrielsson for many stimulating discussions about this chapter.

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Authors and Affiliations

  1. Mathematical Institute, Leiden University, Leiden, The Netherlands

    Lambertus A. Peletier

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  1. Lambertus A. Peletier
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Correspondence to Lambertus A. Peletier .

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  1. Insilico Medicine Hong Kong Ltd, Pak Shek Kok, Hong Kong

    Quentin Vanhaelen

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Peletier, L.A. (2022). An Extended Model Including Target Turnover, Ligand–Target Complex Kinetics, and Binding Properties to Describe Drug–Receptor Interactions. In: Vanhaelen, Q. (eds) Computational Methods for Estimating the Kinetic Parameters of Biological Systems. Methods in Molecular Biology, vol 2385. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1767-0_2

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  • DOI: https://doi.org/10.1007/978-1-0716-1767-0_2

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1766-3

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