期刊
JOURNAL OF THEORETICAL BIOLOGY
卷 256, 期 2, 页码 253-262出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2008.09.014
关键词
Plasma-protein binding; Receptor occupancy; Modelling complex systems behaviours; Time scales; Analytical descriptions
In this paper we analyse the dynamics of an inhibitor I which can either bind to a receptor R or to a plasma protein P. Assuming typical association and dissociation rates, we find that after an initial dose of inhibitor, there are three time scales: a short one, measured in fractions of seconds, in which the inhibitor concentration and the plasma-protein complex jump to quasi-stationary values, a medium one, measured in seconds in which the receptor complex rises to an equilibrium value and a large one, measured in hours in which the inhibitor-receptor complex slowly drops down to zero. We show that the average receptor occupancy, the pharmacologically relevant quantity, taken over, say, 24 h reaches a maximal value for a specific value of the plasma-protein binding constant. Potentially, understanding and exploiting this optimum could be of great interest to those involved in drug discovery and development. (C) 2008 Elsevier Ltd. All rights reserved.
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