Volume of distribution

In pharmacology, the volume of distribution (${\displaystyle V_{D}}$, also known as apparent volume of distribution or volume of dilution¹) is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.²

Roughly speaking, the ${\displaystyle V_{D}}$, as a property of a drug, measures the degree to which it is distributed in body tissue rather than the blood plasma. Drug properties which cause high ${\displaystyle V_{D}}$ include high lipid solubility (non-polarity), low rates of ionization, or low plasma protein binding capabilities. Disease states which increase ${\displaystyle V_{D}}$ include kidney failure (due to fluid retention) and liver failure (due to altered body fluid and plasma protein binding). Conversely, dehydration may decrease ${\displaystyle V_{D}}$.

The initial volume of distribution describes blood concentrations prior to attaining the apparent volume of distribution and uses the same formula.

Suppose one administers an amount of drug ${\displaystyle D}$ intravascularly, then measures the drug concentration in blood ${\displaystyle C_{0}}$ (assuming enough time has elapsed for the drug to distribute, but not enough time for elimination). The volume of distribution is the quotient:

${\displaystyle V_{D}={\frac {D}{C_{0}}}}$

If the drug remains entirely intravascularly, ${\displaystyle V_{D}}$ will be identical to the blood volume ${\displaystyle V_{blood}}$. However, if a drug diffuses out of the intravascular space into the tissues or interstitium, the measured concentration will be lower-than-expected compared to a hypothetical intravascular-only drug. Therefore, ${\displaystyle V_{D}>V_{blood}}$, with a higher ${\displaystyle V_{D}}$ value corresponding to a greater tendency for the drug to exit the intravascular space.

One clinical utility is that the dose required ${\displaystyle D}$ to achieve a target plasma concentration ${\displaystyle C_{0}}$ can be determined if the ${\displaystyle V_{D}}$ for that drug is known.

The ${\displaystyle V_{D}}$ is not a physiological value; it is more a reflection of how a drug will distribute throughout the body depending on several physicochemical properties such as solubility, charge, size, etc.

The unit for ${\displaystyle V_{D}}$ may be reported extensively in litres (for a patient of given weight), or intensively as litres-per-kilogram.

The ${\displaystyle V_{D}}$ may also be used to determine how readily a drug will displace into the body tissue compartments relative to the blood:

${\displaystyle {V_{D}}={V_{P}}+{V_{T}}\left({\frac {f_{u_{P}}}{f_{u_{T}}}}\right)}$

Where:

• ${\displaystyle V_{P}}$: plasma volume
• ${\displaystyle V_{T}}$: apparent tissue volume
• ${\displaystyle f_{u_{P}}}$: fraction unbound in plasma
• ${\displaystyle f_{u_{T}}}$: fraction unbound in tissue

For example, chloroquine has much greater affinity for body fat than blood, resulting in a ${\displaystyle V_{D}\approx 250L/kg}$ ³ compared to ${\displaystyle V_{blood}\approx 0.08L/kg}$.⁴

Example ${\displaystyle V_{D}}$ values for a 70 kg man,⁵ with approximate blood volume 5-6L.

Drug	${\displaystyle V_{D}}$	Comments
Warfarin	8 L	Reflects a high degree of plasma protein binding, which sequesters the drug in the intravascular space.
Theophylline, Ethanol	30 L	Represents distribution in total body water.
Chloroquine	15000 L	Shows highly lipophilic molecules which sequester into total body fat.
NXY-059	8 L	Highly charged hydrophilic molecule.