In pharmacology, the volume of distribution (π {\displaystyle V_{D}}
, also known as apparent volume of distribution or volume of dilution[1]) 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 π {\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 π {\displaystyle V_{D}}
include high lipid solubility (non-polarity), low rates of ionization, or low plasma protein binding capabilities. Disease states which increase π {\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 π {\displaystyle V_{D}}
.
The initial volume of distribution describes blood concentrations prior to attaining the apparent volume of distribution and uses the same formula.
Motivation and equation
[edit]Suppose one administers an amount of drug π {\displaystyle D}
intravascularly, then measures the drug concentration in blood π {\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:
π {\displaystyle V_{D}={\frac {D}{C_{0}}}}
If the drug remains entirely intravascularly, π {\displaystyle V_{D}}
will be identical to the blood volume π {\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, π {\displaystyle V_{D}>V_{blood}}
, with a higher π {\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 π {\displaystyle D}
to achieve a target plasma concentration π {\displaystyle C_{0}}
can be determined if the π {\displaystyle V_{D}}
for that drug is known.
The π {\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 π {\displaystyle V_{D}}
may be reported extensively in litres (for a patient of given weight), or intensively as litres-per-kilogram.
The π {\displaystyle V_{D}}
may also be used to determine how readily a drug will displace into the body tissue compartments relative to the blood:
Where:
- π {\displaystyle V_{P}}
: plasma volume - π {\displaystyle V_{T}}
: apparent tissue volume - π {\displaystyle f_{u_{P}}}
: fraction unbound in plasma - π {\displaystyle f_{u_{T}}}
: fraction unbound in tissue
Examples
[edit]For example, chloroquine has much greater affinity for body fat than blood, resulting in a π {\displaystyle V_{D}\approx 250L/kg}
[3] compared to π {\displaystyle V_{blood}\approx 0.08L/kg}
.[4]
| Drug | π {\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. |
References
[edit]- ^ Ward RM, Kern SE, Lugo RA (2012). "Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics". Avery's Diseases of the Newborn. Elsevier. pp. 417β428. doi:10.1016/b978-1-4377-0134-0.10034-4. ISBN 978-1-4377-0134-0.
- ^ "Volume of distribution". sepia.unil.ch. Retrieved 19 April 2018.
- ^ Wetsteyn JC, De Vries PJ, Oosterhuis B, Van Boxtel CJ (June 1995). "The pharmacokinetics of three multiple dose regimens of chloroquine: implications for malaria chemoprophylaxis". British Journal of Clinical Pharmacology. 39 (6): 696β699. doi:10.1111/j.1365-2125.1995.tb05731.x. PMC 1365086. PMID 7654492.
- ^ Alberts B (2005). "Leukocyte functions and percentage breakdown". Molecular Biology of the Cell. Retrieved 2007-04-14 β via NCBI Bookshelf.
- ^ Swain C. "Distribution and plasma protein binding". Cambridge MedChem Consulting. Retrieved 2020-04-02.
