Receptor-binding kinetics model

S. Wanant, M.f. Quon, Insulin receptor binding kinetics modeling and simulation studies, J. Theor. Biol. 2000, 205, 355-364. 

The choice of model should be based on biological, physiological, and pharmacokinetic plausibility. For example, compartmental models may be used because of their basis in theory and plausibility. It is easy to conceptualize that a drug that distributes more slowly into poorly perfused tissues than rapidly perfused tissues will show multi-phasic concentration-time profiles. Alternatively, the Emax equation, one of the most commonly used equations in pharmacodynamic modeling, can be developed based on mass balance principles and receptor binding kinetics. 

Hirschberg, B. T. and Schimerlik, M. I. (1994) A kinetic model for oxotremorine M binding to recombinant porcine m2 muscarinic receptors expressed in Chinese hamster ovary cells../. Biol. Chem. 269,26127-26135. 

A detailed quantitative evaluation of tracer kinetics requires the use of compartment modelling. A two-tissue compartment model is used for the evaluation of the dynamic studies. This is a standard methodology in particular for the quantification of dynamic FDG studies (13-15). Concerning the 68Ga-peptide kinetics, again the two-tissue compartment model is applied to the data. In case of 68Ga-labelled peptides, DOTATOC or bombesin, kl is associated with the receptor binding, k2 with the displacement from the receptor, k3 with the cellular internalisation, and k4 with the externalisation. The fractional blood volume... 

M. Weiss and W. Kang, Inotropic effect of digoxin in humans mechanistics pharmaco-kinetic/pharmacodynamic model based on slow receptor binding. Pharm Res 21 231-236 (2004). 

A constant and homogeneous concentration of free analyte represents the ideal condition for modeling molecular interactions at the surface of an SPR biosensor. In the most frequent case where an analyte binds to an immobilized receptor with 1 1 stoichiometry, the interaction follows the pseudo first-order kinetic model. Adequate interaction models can be built up to describe more complex molecular interactions some of them have been presented and explained above. 

We have developed a preliminary kinetic model of the interleukin 1 (IL-1)-stimulated intracellular signaling pathway in epidermal keratinocytes as an initial effort toward the pharmacodynamic modeling of the skin. On exposure to external stimuli, such as chemical irritants, the skin secretes various cytokines and chemo-kines and evokes a cascade of events in the subcutaneous tissue. Therefore, the pharmacodynamic process of the skin primarily involves the responses of the skin cells to these endogenous proteins. Among them, one of central importance is IL-1, a proinflammatory cytokine that mediates the host defense activities of the skin. The model captures the series of biochemical events initiated from IL-1 a binding to IL-1 receptor (type I) on the cell surface that activates the transcriptional factor nuclear factor (NFk-B) and leads to production of a responsive protein, IL-6, as illustrated in Figure 6.6. 

Destexhe, A., Z.F. Mainen, and T.). Sejnowski (1994). An efficient method for computing synaptic conductances based on a kinetic model of receptor binding. Neural Comput. 6,14—18. 

Additionally, more sophisticated models exist which include drug release and ligand-receptor binding [36,42]. For instance, in Haun and Hammer [42], a rate equation was used to model the kinetics of nanoparticle adhesion via ligand-receptor binding ... 

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