Vdss

Vdss, the volume of distribution at steady state, is a pharmacokinetic parameter that quantifies how extensively a drug distributes into body tissues relative to the plasma once equilibrium between compartments has been achieved. It is defined as the amount of drug in the body at steady state divided by the plasma concentration at steady state: Vdss = A(ss) / Cpss. It can also be expressed as Vdss = CL × MRT, where MRT (mean residence time) = AUMC / AUC.

Interpretation of Vdss is nuanced. A small Vdss suggests the drug largely remains in the plasma, while a large Vdss indicates extensive distribution into tissues. Vdss is not a physical organ or space; it is a theoretical volume that may exceed body water or even body volume for drugs that heavily bind to tissues or accumulate in fat, liver, or other organs.

Estimation and calculation. Vdss is typically estimated from plasma concentration–time data after intravenous dosing using noncompartmental analysis, requiring measurements of the area under the curve (AUC), the area under the first moment curve (AUMC), and clearance (CL). In compartmental models, Vdss is derived from model parameters. In practice, Vdss is often larger than the initial distribution volume (Vd) for multi-compartment kinetics, reflecting slower equilibration with deep tissue stores.

Clinical relevance and applications. Vdss informs loading dose computations: loading dose ≈ target concentration × Vdss. It helps explain how factors such as obesity, edema, age, liver or kidney disease, and drug lipophilicity affect distribution and dosing. Changes in Vdss can alter achieved plasma concentrations and therapeutic effects.