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Theoretical drug measure in pharmacology

In pharmacology, the volume of distribution (πŸ‘ {\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 πŸ‘ {\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 πŸ‘ {\displaystyle V_{D}}
include high lipid solubility (non-polarity), low rates of ionization, or low plasma protein binding capabilities. Disease states which increase πŸ‘ {\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 πŸ‘ {\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

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Suppose one administers an amount of drug πŸ‘ {\displaystyle D}
intravascularly, then measures the drug concentration in blood πŸ‘ {\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:

πŸ‘ {\displaystyle V_{D}={\frac {D}{C_{0}}}}

If the drug remains entirely intravascularly, πŸ‘ {\displaystyle V_{D}}
will be identical to the blood volume πŸ‘ {\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, πŸ‘ {\displaystyle V_{D}>V_{blood}}
, with a higher πŸ‘ {\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 πŸ‘ {\displaystyle D}
to achieve a target plasma concentration πŸ‘ {\displaystyle C_{0}}
can be determined if the πŸ‘ {\displaystyle V_{D}}
for that drug is known.

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

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

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

Where:

Examples

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

Example πŸ‘ {\displaystyle V_{D}}
values for a 70 kg man,[5] with approximate blood volume 5-6L.
Drug πŸ‘ {\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

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  1. ^ Ward RM, Kern SE, Lugo RA (2012). "Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics". Avery's Diseases of the Newborn. Elsevier. pp. 417–428. doi:10.1016/b978-1-4377-0134-0.10034-4. ISBN 978-1-4377-0134-0.
  2. ^ "Volume of distribution". sepia.unil.ch. Retrieved 19 April 2018.
  3. ^ 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): 696–699. doi:10.1111/j.1365-2125.1995.tb05731.x. PMC 1365086. PMID 7654492.
  4. ^ Alberts B (2005). "Leukocyte functions and percentage breakdown". Molecular Biology of the Cell. Retrieved 2007-04-14 – via NCBI Bookshelf.
  5. ^ Swain C. "Distribution and plasma protein binding". Cambridge MedChem Consulting. Retrieved 2020-04-02.

External links

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