Central Volume

For one-compartment models, Central Volume, notated \(V\), is the volume of distribution of the drug. For multi-compartment models, \(V\) represents the peripheral blood plasma, where drug concentrations are most commonly measured to describe pharmacokinetics.

In the case of ADCs, the Central Volume of both conjugated antibody and payload are assumed to be equal for simplicity.

Setting the Model Value

Antibodies, antibody-like molecules, and large protein biotherapeutics are generally restricted to the extracellular spaces in the body. In the peripheral blood, protein biotherapeutics are restricted to the non-cellular or plasma fraction.

For a one-compartment model, the compartment volume is defined as the volume of distribution. Antibodies and antibody-based biotherapeutics generally display consistent pharmacokinetic behavior, and the volume of distribution can be set to typical values. If pharmacokinetic data or parameters for a 2-compartment pharmacokinetic model are reported for a molecule, the reported volume of distribution can be used.

For a multi-compartment model, the central compartment volume is defined as plasma volume. Typical values for plasma volume of human or commonly used preclinical species are listed below. If pharmacokinetic data or parameters for a 2-compartment pharmacokinetic model are reported for a molecule, the reported central compartment volume can be used.

Typical Values

In humans, the typical volume of distribution for an antibody is 5.2 L (Dirks et al.). For multi-compartment models of antibody or antibody-like biotherapeutics, the central compartment volume can be defined as the plasma volume. Plasma volumes for human and commonly used preclinical species are listed below:

Species	Volume	Reference
Human (antibody volume of distribution)	5.2 (L)	Dirks et. al, Davada et. al., Betts et. al.
Human	3 (L)	Davies et. al
Cynomologous Monkey	0.123 - 0.258 (L)	Ageyama et. al
Rat	0.0078 (L)	Davies et. al
Mouse	0.001 (L)	Davies et. al