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A Mathematical Analysis of Rebound in a Target-Mediated Drug Disposition Model. II. With Feedback

Aston, PJ, Derks, G., Agoram, BM and van der Graaf, PH (2016) A Mathematical Analysis of Rebound in a Target-Mediated Drug Disposition Model. II. With Feedback Journal of Mathematical Biology.

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Abstract

We consider the possibility of free receptor (antigen/cytokine) levels rebounding to higher than the baseline level after the application of an antibody drug using a target-mediated drug disposition model. It is assumed that the receptor synthesis rate experiences homeostatic feedback from the receptor levels. It is shown for a very fast feedback response, that the occurrence of rebound is determined by the ratio of the elimination rates, in a very similar way as for no feedback. However, for a slow feedback response, there will always be rebound. This result is illustrated with an example involving the drug efalizumab for patients with psoriasis. It is shown that slow feedback can be a plausible explanation for the observed rebound in this example.

Item Type: Article
Subjects : Maths
Divisions : Faculty of Engineering and Physical Sciences > Mathematics
Authors :
NameEmailORCID
Aston, PJUNSPECIFIEDUNSPECIFIED
Derks, G.UNSPECIFIEDUNSPECIFIED
Agoram, BMUNSPECIFIEDUNSPECIFIED
van der Graaf, PHUNSPECIFIEDUNSPECIFIED
Date : 10 November 2016
Identification Number : 10.1007/s00285-016-1073-6
Copyright Disclaimer : © The Author(s) 2016. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Depositing User : Symplectic Elements
Date Deposited : 27 Oct 2016 14:45
Last Modified : 20 Jul 2017 08:51
URI: http://epubs.surrey.ac.uk/id/eprint/812644

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