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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 (2013) A mathematical analysis of rebound in a target-mediated drug disposition model: I.Without feedback. J Math Biol, 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.

Item Type: Article
Divisions : Faculty of Engineering and Physical Sciences > Mathematics
Authors :
AuthorsEmailORCID
Aston, PJUNSPECIFIEDUNSPECIFIED
Derks, GUNSPECIFIEDUNSPECIFIED
Agoram, BMUNSPECIFIEDUNSPECIFIED
van der Graaf, PHUNSPECIFIEDUNSPECIFIED
Date : 17 April 2013
Identification Number : 10.1007/s00285-013-0675-5
Related URLs :
Additional Information : The original publication is available at http://www.springerlink.com
Depositing User : Symplectic Elements
Date Deposited : 09 Aug 2013 09:12
Last Modified : 09 Jun 2014 13:53
URI: http://epubs.surrey.ac.uk/id/eprint/792107

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