Can happen if the parent is displaced from the binding sites by the additionally administered parent, especially if there are a lot of binding sites in large organs like liver.

I have seen this with radiolabelled parent getting displaced by unlabelled parent, leading to an increase in the plasma concentration of the radiolabelled parent. Since there is more radiolabelled parent in the plasma, it can also get metabolised to give more radiometabolites.

Nisha Kuzhuppilly Ramakrishnan thank you. Your observation would justify and sink. Similarly I noticed an increase in non-radiolabelled parent (tracer) level in few of our occupancy assays.

Please correct my understanding on your case, unlabelled parent will be administered first followed by radiolabelled parent (tracer). In that case the left over binding sites can be bound by the radiolabelled parent. Moreover the tracer dose is very low compared to unlabelled parent. Then how can a displacement of radiolabelled parent takes place?

Is that your observation need to be addressed with respect to impact of unlabelled parent on metabolism of labelled parent (tracer)? Kindly clarify

I am not sure I understand your question.

My experience is with reversible binders. If your compound has reversible binding, there will be an equilibrium to the association and dissociation from the target. It is not only the 'left over' sites that are involved.

When the unlabelled compound is in excess to the labelled compound, there is a comparatively larger amount of unlabelled parent in the plasma available to bind to any available site. Since there is more of the unlabelled compound available in the plasma, it is more likely for the unlabelled compound to bind to the target than the labelled compound which is in lower concentration in the plasma. This means in this situation there will be a larger amount of labelled compound in the plasma than in a situation where unlabelled compound was not administered.

When only the labelled compound is administered and all sites are available to bind, more of the labelled compound will be bound to the target, there will be less of the labelled compound in the plasma.

If there is more of the labelled compound in the plasma, it is then available to be metabolised than if it was bound to the target.

Hope this helps.