Volume of distribution
The volume of distribution (VD) , also known as apparent volume of distribution, is a pharmacological term used to quantify the distribution of a medication between plasma and the rest of the body after oral or parenteral dosing. It is defined as the volume in which the amount of drug would need to be uniformly distributed to produce the observed blood concentration. [1]
Volume of distribution may be increased by renal failure (due to fluid retention) and liver failure (due to altered body fluid and plasma protein binding). Conversely it may be decreased in dehydration.
The initial volume of distribution describes blood concentrations prior to attaining the apparent volume of distribution and uses the same formula.
Equations
The volume of distribution is given by the following equation:
- <math>{V_{D}} = \frac{\mathrm{total \ amount \ of \ drug \ in \ the \ body}}{\mathrm{drug \ blood \ plasma \ concentration}}</math>
Therefore the dose required to give a certain plasma concentration can be determined if the VD for that drug is known. The VD is not a physiologic value; it is more a reflection of how a drug will distribute throughout the body depending on several physicochemical properties, e.g. solubility, charge, size, etc.
The units for Volume of Distribution are typically reported in (ml or liter)/kg body weight. The fact that VD is a ratio of a theoretical volume to a fixed unit of body weight explains why the VD for children is typically higher than that for adults, even though children are smaller and weigh less. As body composition changes with age, VD decreases.
The VD may also be used to determine how readily a drug will displace into the body tissue compartments relative to the blood:
- <math>{V_{D}} = {V_{P}} + {V_{T}} \left(\frac{fu}{fu_{t}}\right)</math>
Where:
- VP = plasma volume
- VT = apparent tissue volume
- fu = fraction unbound in plasma
- fuT = fraction unbound in tissue
Examples
Further reading: Table of volume of distribution for drugs
Drug | VD | Comments |
Warfarin | 8L | Reflects a high degree of plasma protein binding. |
Theophylline, Ethanol | 30L | Represents distribution in total body water. |
Chloroquine | 15000L | Shows highly lipophilic molecules which sequester into total body fat. |
NXY-059 | 8L | Highly-charged hydrophilic molecule. |
Sample values and equations
Variable | Description | Example value | Abbreviation(s) | Formula |
---|---|---|---|---|
Dose | loading dose (LD), or steady state/maintenance dose (MD) | 1000 mg | <math>\textstyle D </math> | <math>\textstyle = V_{d} \times C_{0}</math> |
Volume of distribution | The apparent volume in which a drug is distributed immediately after it has been injected intravenously and equilibrated between plasma and the surrounding tissues. | 25 L | <math>\textstyle V_d</math> | <math>\textstyle = D / C_0</math> |
Concentration | initial or steady-state concentration of drug in plasma | 40.0 mg/L | <math>\textstyle C_{0} \ or \ C_{ss}</math> | <math>\textstyle = D / V_d</math> |
Biological half-life | The time required for the concentration of the drug to reach half of its original value. | 14 hr | <math>\textstyle T_{1/2}</math> | <math>\textstyle = ln (2) / K_{e}</math> |
Elimination rate constant | The rate at which drugs are removed from the body. | 0.05 /hr | <math>\textstyle K_e</math> | <math>\textstyle = ln (2) / T_{1/2} = Cl / V_{d}</math> |
Elimination rate | rate of infusion required to balance elimination | 50 mg/hr | <math>\textstyle K_{in}</math> | <math>\textstyle = C_{ss} \times Cl</math> |
Area under the curve | The integral of the plasma drug concentration (Cp) after it is administered. | 0.1 mg/mL×hr | <math>\textstyle AUC_{0\ \infty}</math> | <math>= \int_{0}^{\infty}C_p\, dt</math> |
Clearance | The volume of plasma cleared of the drug per unit time. | 1.25 L/hr | <math>\textstyle Cl</math> | <math>\textstyle= V_{d} \times K_{e} = D/AUC</math> |
Bioavailability | The fraction of drug that is absorbed. | 1 | <math>\textstyle F</math> | <math>= \frac{[AUC]_{intravenous}\times dose_{oral}}{[AUC]_{oral}\times dose_{intravenous}}</math> |
Cmax | The peak plasma concentration of a drug after oral administration. | 40.0 mg/L | <math>\textstyle C_{max}</math> | direct measurement |
Cmin | The lowest (trough) concentration that a drug reaches before the next dose is administered. | 1.0 mg/L | <math>\textstyle C_{min}</math> | direct measurement |
edit |
where ln(2) = 0.69315...
References
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External links
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