Dynamics of a two-receptor binding model: How affinities and capacities translate      into long and short time behaviour and physiological corollaries

Lambertus A. Peletier; Willem de Winter; An Vermeulen

doi:10.3934/dcdsb.2012.17.2171

Article Contents

2012, Volume 17, Issue 6: 2171-2184. Doi: 10.3934/dcdsb.2012.17.2171

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Dynamics of a two-receptor binding model: How affinities and capacities translate into long and short time behaviour and physiological corollaries

1.
Mathematical Institute, Leiden University, PB 9512, 2300 RA Leiden
2.
Advanced Modeling & Simulation; Clinical Pharmacology, Janssen Research & Development, a division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse

Received: June 30, 2011

Revised: January 31, 2012

Published: August 2012

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Abstract

In this paper we present a mathematical analysis of a model involving target-mediated drug disposition involving two targets, developed to fit a series of data sets. The two targets are receptors with very different characteristics: one has high affinity to the drug, a small capacity and a short half-life, whilst the other receptor has low affinity to the drug, high capacity and its half-life is large. The analysis of this model yields a qualitative and quantitative understanding of the dynamics of this two-receptor model and in particular identifies different time scales over which the amounts of free drug and drug-receptor complexes vary. Thus it yields analytical tools to make long-term predictions on the basis of medium term data sets.

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Mathematics Subject Classification: Primary: 34C20, 34D15; Secondary: 92C42, 92C45, 80A30.

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