Volume of distribution

Motivation and equation

Suppose one administers an amount of drug D intravascularly, then measures the drug concentration in blood 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:

V_D = \frac{D}{C_0}

If the drug remains entirely intravascularly, V_D will be identical to the blood volume 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, V_DV_{blood}, with a higher V_D value corresponding to a greater tendency for the drug to exit the intravascular space.

One clinical utility is that the dose required D to achieve a target plasma concentration C_0 can be determined if the V_D for that drug is known.

The 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 V_D may be reported extensively in litres (for a patient of given weight), or intensively as litres-per-kilogram.

The V_D may also be used to determine how readily a drug will displace into the body tissue compartments relative to the blood:

:::::::{V_{D}} = {V_{P}} + {V_{T}} \left(\frac{f_{u_P}}{f_{u_T}}\right)

Where:

• V_P: plasma volume
• V_T: apparent tissue volume
• f_{u_P}: fraction unbound in plasma
• f_{u_T}: fraction unbound in tissue

Examples

Main article: Table of volume of distribution for drugs

For example, chloroquine has much greater affinity for body fat than blood, resulting in a V_D\approx250L/kg compared to V_{blood}\approx 0.08L/kg.

References

References

1. (2012). "Avery's Diseases of the Newborn". Elsevier.
2. "Volume of distribution".
3. (June 1995). "The pharmacokinetics of three multiple dose regimens of chloroquine: implications for malaria chemoprophylaxis". British Journal of Clinical Pharmacology.
4. (2005). "Molecular Biology of the Cell".
5. "Distribution and plasma protein binding".