Impact of protein binding on receptor occupancy: A two-compartment model

Lambertus A. Peletier (1) , Neil Benson , Piet H. van Der Graaf

1 Universiteit Leiden = Leiden University

In this paper we analyse the impact of protein- and lipid- and receptor-binding on receptor occupancy in a two-compartment system, with proteins in both compartments and lipids and receptors in the peripheral compartment only. We do this for two manners of drug administration: a bolus administration and a constant rate infusion, both into the central compartment. We derive explicit approximations for the time-curves of the different compounds valid for a wide range of realistic values of rate constants and initial concentrations of proteins, lipids, receptors and the drug. These approximations are used to obtain both qualitative and quantitative insight into such critical properties as the distribution of the drug over the two compartments, the maximum receptor occupancy and the area under the drug-receptor complex curve. In particular we focus on assessing the impact of the dissociation constants, K, K and K of the drug with, respectively, the proteins, the lipids and the receptors, the permeability and the surface area of the membrane between compartments, and the rate the drug is eliminated from the system.

Mots clés: Plasma-protein binding; Receptor occupancy; Modelling complex systems behaviours; Time scales; Analytical descriptions; Blood-brain barrier

Lambertus A. Peletier, Neil Benson, Piet H. van Der Graaf. Impact of protein binding on receptor occupancy: A two-compartment model. Journal of Theoretical Biology, 2010, 265 (4), pp.657. ⟨10.1016/j.jtbi.2010.05.035⟩. ⟨hal-00608944⟩