Visualizing the effects of plasma protein binding, tissue binding and membrane permeability of volume of distribution

The volume of distribution of any drug depends on a number of variables, body weight (affecting absolute physical volume of the tissues), plus the relative affinity of the drug molecule for the tissues. Traditionally the latter has been viewed as being a function of plasma protein binding and tissue binding. Nowadays however, with the increasing appreciation of the importance of membrane transporter proteins in determining permeability into tissue compartments, it is better to view distribution as being affected by a composite variable that emcompasses plasma and tissue binding as well as the net permeability across tissue membrane barriers.

Try and imagine how inter-subject differences in these variables can ultimately affect drug disposition and drug response.

Tissue Binding: 0.3

Protein Binding: 0.7

Tissue %: 0.4

Permeability: 1