Volume of Distribution

• Volume of distribution (V_d) is the ratio between the amount of drug in body (dose given) and the concentration of the drug (C) measured in blood or plasma.

  • V_d = (amount of drug in body)/C where C is the concentration of drug in blood or plasma.

  • V_d as calculated is an apparent volume of distribution. For example:

    • V_d for digoxin is 440 L/70 kg (liters per 70 kg person)

    • V_d for chloroquine is 13,000 L/70 kg (liters per 70 kg person)

    • Such very large V_d would be consistent with very high tissue binding, leaving little free in plasma or blood

  • V_d is an apparent volume of distribution, since V_d is the volume needed to contain the amount of drug homogeneously at the concentration found in the blood, plasma, or plasma water.

    • Many drugs have a much higher concentration in extravascular compartments; therefore these drugs are NOT homogeneously distributed.

• Physical volumes (L./kg body weight) for some body compartments

  • Water

    • Total Body Water (0.5-0.7 L/kg) or about 35000 to 49000 ml (70 kg individual)

    • Extracellular Water (0.2 L./kg)

    • Blood (0.08 L./kg);

    • Plasma (0.04 L./kg)

  • Fat

    • 0.2 - 0.35 L./kg 

  • Bone

    • 0.07 L/kg

• Factors influencing the volume of distribution:

  • Drug pK_a

  • Extent of drug-plasma protein binding

  • Partition coefficient of the drug in fat (lipid solubility)

  • V_d may be affected by:

    • Patient's gender

    • Patient's age

    • Patient's disease

    • Patient's body composition

  • Example of a poorly lipid soluble agent with a V_d about equal to extracellular fluid volume: nondepolarizing neuromuscular blocking drugs.