Volume of distribution (V)
The volume of distribution relates the amount of drug in the body to its plasma concentration. In compartment models, V1 is the central volume and V2 the peripheral volume. It is a proportionality, not a physical volume.
Definition
The volume of distribution (V) is the amount of drug in the body divided by the plasma concentration. It is the volume that the body would need if the drug were at the plasma concentration everywhere. A drug that binds tissue strongly has a large V.
Compartment models
In a two-compartment model, V1 is the central volume (plasma and fast-equilibrating tissue) and V2 the peripheral volume. Vss is the steady-state volume, V1 + V2 for a two-compartment model.
Antibodies
Monoclonal antibodies have small volumes, of the order of a few liters for V1. In the published models re-implemented on this site, pembrolizumab has V1 = 3.48 L and V2 = 4.06 L, and nivolumab V1 = 3.63 L and V2 = 2.78 L (see the anti-PD-1 analysis).
Relation to half-life
For a one-compartment model, the half-life is ln 2 × V / CL; see half-life. The tarlatamab analysis asks how well four parameters, including the volumes, can be identified from published summary values.
Frequently asked questions
Is the volume of distribution a real volume?
No. It is a proportionality between amount and concentration, and it can exceed the volume of the body for drugs that bind tissue extensively.
What is the difference between V1 and Vss?
V1 is the central volume of a compartment model; Vss is the total volume at steady state, V1 + V2 in a two-compartment model.