Volume of distribution pharma
Reading File
Finding Sources
Searching PubMed
"volume of distribution" AND pharmacokinetics
Searching the Web
volume of distribution pharmacokinetics FDA glossary
Reading File
Volume of distribution (Vd)
Volume of distribution is the apparent volume that would be required to contain the total amount of drug in the body at the same concentration measured in plasma.
[
\boxed{V_d = \frac{\text{Amount of drug in body}}{\text{Plasma drug concentration }(C_p)}}
]
For an IV bolus dose:
[
\boxed{V_d = \frac{\text{Dose}}{C_0}}
]
Where (C_0) is the extrapolated initial plasma concentration.
Key point
Vd is not necessarily a real anatomical volume. A drug may have a Vd far greater than total body volume because it leaves plasma and binds extensively to tissues.
Interpretation
| Vd | Meaning |
|---|---|
| Low Vd | Drug remains mainly in blood/plasma |
| About 3-5 L | Mostly confined to plasma |
| About 10-20 L | Mainly in extracellular fluid |
| About 40 L | Distributed roughly throughout total body water |
| Very large Vd, >40 L | Extensive tissue or fat binding, low plasma concentration |
What increases Vd?
- High lipid solubility
- Extensive tissue binding
- Low plasma-protein binding
- Edema, ascites, or pleural effusion for hydrophilic drugs
For example, edema or ascites can markedly increase Vd of hydrophilic drugs such as gentamicin. Tissue binding lowers plasma concentration and therefore increases apparent Vd, whereas plasma-protein binding tends to retain drug in plasma and lowers Vd. Katzung's Basic and Clinical Pharmacology, 16th ed., p. 88.
Examples
- Warfarin: low Vd because it is highly plasma-protein bound.
- Gentamicin: relatively low Vd, largely extracellular distribution; Vd rises in edema/ascites.
- Digoxin: large Vd because of tissue, especially skeletal muscle, binding.
- Chloroquine: extremely large Vd due to extensive tissue sequestration.
Clinical importance
- Calculating loading dose
[
\boxed{\text{Loading dose} = \frac{V_d \times \text{Target plasma concentration}}{F}}
]
Where (F) is bioavailability. For IV administration, (F=1).
-
Predicting dialysis removal
Drugs with a small Vd remain in plasma and are generally more dialyzable. Drugs with a large Vd are extensively in tissues and usually poorly removed by dialysis. -
Relation to half-life
[
\boxed{t_{1/2} = \frac{0.693 \times V_d}{CL}}
]
At the same clearance (CL), a higher Vd produces a longer half-life.
- Dose adjustment in altered body composition
Age, obesity, fluid overload, and muscle wasting can change Vd and affect loading-dose requirements.
This is a shared conversation. Sign in to Orris to start your own chat.