Receptor occupancy (RO)
Receptor occupancy is the fraction of target receptors bound by a drug. For simple binding it follows RO = C / (C + Kd), and it is a step between drug concentration and pharmacological effect.
Definition
Receptor occupancy (RO) is the fraction of the target receptors that are bound by the drug. For simple, reversible, one-to-one binding at equilibrium, RO = C / (C + Kd), where C is the free drug concentration and Kd the dissociation constant: at C = Kd, half of the receptors are occupied.
Competition
If another ligand, or residual drug from a previous dose, also binds the target, binding is competitive and the occupancy by the new dose is lower at the same concentration. Models of step-up dosing use this to describe how earlier doses affect the occupancy by later ones.
Role in PK/PD
Occupancy is a step between the concentration and the pharmacological effect. It can link PK to a response such as cytokine release syndrome only if each link is supported by data.
On this site
The mosunetuzumab reimplementation includes the CD20 binding equation with competitive binding and separates the steps from dose to PK, from PK to occupancy and from occupancy to cytokine release syndrome, reporting what public information supports at each step.
Frequently asked questions
What does Kd mean?
The dissociation constant, the concentration at which half of the receptors are occupied at equilibrium.
Is high occupancy the same as a strong effect?
Not necessarily. The effect depends on what the occupancy triggers, and the relationship between occupancy and effect has to be established separately.