MURAL - Maynooth University Research Archive Library



    Nonlinear pharmacokinetics of therapeutic proteins resulting from receptor mediated endocytosis


    Krippendorff, Ben-Fillippo and Kuester, Katharina and Kloft, Charlotte and Huisinga, Wilhelm (2009) Nonlinear pharmacokinetics of therapeutic proteins resulting from receptor mediated endocytosis. Journal of Pharmacokinetics and Pharmacodynamics , 36 (3). pp. 239-260. ISSN 1567-567X

    [img] Download (735kB)
    Official URL: http://www.springerlink.com/content/c7202j8766080j...


    Share your research

    Twitter Facebook LinkedIn GooglePlus Email more...



    Add this article to your Mendeley library


    Abstract

    Receptor mediated endocytosis (RME) plays a major role in the disposition of therapeutic protein drugs in the body. It is suspected to be a major source of nonlinear pharmacokinetic behavior observed in clinical pharmacokinetic data. So far, mostly empirical or semi-mechanistic approaches have been used to represent RME. A thorough understanding of the impact of the properties of the drug and of the receptor system on the resulting nonlinear disposition is still missing, as is how to best represent RME in pharmacokinetic models. In this article, we present a detailed mechanistic model of RME that explicitly takes into account receptor binding and trafficking inside the cell and that is used to derive reduced models of RME which retain a mechanistic interpretation. We find that RME can be described by an extended Michaelis–Menten model that accounts for both the distribution and the elimination aspect of RME. If the amount of drug in the receptor system is negligible

    Item Type: Article
    Additional Information: The original publication is available at http://www.springerlink.com/content/c7202j8766080j31/fulltext.pdf
    Keywords: Recepter mediated endocytosis; Nonlinear pharmacokinetics; Michaelis–Menten; Therapeutic proteins; Biopharmaceuticals; Epidermal growth factor receptor; Nonlinear dispostition; Receptor trafficking; Antibodies; Hamilton Institute.
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Chemistry
    Faculty of Science and Engineering > Research Institutes > Hamilton Institute
    Item ID: 1658
    Identification Number: https://doi.org/10.1007/s10928-009-9120-1
    Depositing User: Hamilton Editor
    Date Deposited: 10 Nov 2009 15:18
    Journal or Publication Title: Journal of Pharmacokinetics and Pharmacodynamics
    Publisher: Springer Verlag
    Refereed: Yes
    URI:
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

    Repository Staff Only(login required)

    View Item Item control page

    Downloads

    Downloads per month over past year

    Origin of downloads