Volume of Distribution Interpretation for 6 L/kg
An experimental drug with an apparent volume of distribution (Vd) of 6 L/kg is sequestered in body tissues, indicating extensive extravascular distribution beyond plasma and extracellular fluid compartments.
Understanding Volume of Distribution Values
The volume of distribution provides critical insight into drug distribution patterns based on physiological compartment volumes 1:
- Plasma volume: approximately 0.04-0.05 L/kg
- Extracellular fluid volume: approximately 0.2-0.3 L/kg
- Total body water: approximately 0.6 L/kg
When Vd exceeds total body water (>0.6 L/kg), this indicates the drug is concentrating in tissues beyond simple aqueous distribution 1.
Why 6 L/kg Indicates Tissue Sequestration
A Vd of 6 L/kg is 10-fold greater than total body water, definitively indicating extensive tissue binding and sequestration 1. This large apparent volume occurs when:
- The drug has high lipophilicity and accumulates in cellular lipids 2
- Tissue concentrations substantially exceed plasma concentrations 1
- The drug binds extensively to intracellular components 3
Lipophilic substances that accumulate in cellular compartments demonstrate this pattern of distribution, as documented with compounds like monohydric alcohols, salicylamide, and octanoate in hepatic tissue 2.
Eliminating Other Options
Option (a) - Highly bound to plasma proteins is incorrect: High plasma protein binding actually decreases Vd because the drug remains confined to the vascular space 4, 3. Drugs tightly bound to albumin (like Evans blue dye) have small volumes of distribution 2.
Option (b) - Confined to vascular compartment is incorrect: Vascular compartment volume is only 0.04-0.05 L/kg 1. A drug confined to plasma would have a Vd approximating this value, not 6 L/kg.
Option (d) - Distributed in extracellular fluid volume is incorrect: Extracellular fluid volume is approximately 0.2-0.3 L/kg 1. The observed Vd of 6 L/kg is 20-30 times larger than extracellular fluid volume, indicating distribution far beyond this compartment.
Clinical Implications
Drugs with large volumes of distribution (>1 L/kg) typically exhibit 1, 3:
- Prolonged elimination half-lives due to slow release from tissue depots
- Lower plasma concentrations relative to total body drug content
- Requirement for higher loading doses to achieve therapeutic plasma levels
- Potential for drug accumulation with repeated dosing
Common Pitfall to Avoid
Do not confuse high plasma protein binding with large Vd. These are inversely related: high plasma protein binding restricts distribution and results in smaller Vd values, while low plasma protein binding with high tissue affinity results in larger Vd values 4, 3.