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A mathematical analysis of rebound in a target-mediated drug disposition model: I.Without feedback

Aston, PJ, Derks, G, Agoram, BM and van der Graaf, PH (2014) A mathematical analysis of rebound in a target-mediated drug disposition model: I.Without feedback Journal of Mathematical Biology, 68 (6). pp. 1453-1478.

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Abstract

We consider the possibility of free receptor (antigen/cytokine) levels rebounding to higher than the baseline level after one or more applications of an antibody drug using a target-mediated drug disposition model. Using geometry and dynamical systems analysis, we show that rebound will occur if and only if the elimination rate of the drug-receptor product is slower than the elimination rates of the drug and of the receptor. We also analyse the magnitude of rebound through approximations and simulations and demonstrate that it increases if the drug dose increases or if the difference between the elimination rate of the drug-receptor product and the minimum of the elimination rates of the drug and of the receptor increases. © 2013 Springer-Verlag Berlin Heidelberg.

Item Type: Article
Divisions : Faculty of Engineering and Physical Sciences > Mathematics
Authors :
AuthorsEmailORCID
Aston, PJUNSPECIFIEDUNSPECIFIED
Derks, GUNSPECIFIEDUNSPECIFIED
Agoram, BMUNSPECIFIEDUNSPECIFIED
van der Graaf, PHUNSPECIFIEDUNSPECIFIED
Date : May 2014
Identification Number : 10.1007/s00285-013-0675-5
Additional Information : The original publication is available at http://link.springer.com/article/10.1007%2Fs00285-013-0675-5
Depositing User : Symplectic Elements
Date Deposited : 26 Nov 2014 14:49
Last Modified : 01 Mar 2015 02:35
URI: http://epubs.surrey.ac.uk/id/eprint/806573

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