Medical Pharmacology Chapter 2: General Principles: Pharmacokinetics

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

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

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

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

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

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

• Vd is an apparent volume of distribution, since Vd 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 pKa

• Extent of drug-plasma protein binding

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

• Vd 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 Vd about equal to extracellular fluid volume: nondepolarizing neuromuscular blocking drugs.

•  Semilogarithmic plot above illustrates extrapolation to time 0 required to determine the volume of distribution; Vd = dose/Co- also note that the drug elimination halftime can be directly calculated from the graph. This graph applied for a single compartment model only.  For multiple compartments which will appear as a. non-linear relationship extrapolation back to t = 0 must be performed for each compartment separately.  From Goodman Gilman, A, Rall T, Nies, A, Taylor P, eds Goodman and Gillman:  The Pharmacological Basis of Therapeutics, 8th edn, Oxford: Pergamon, 1990

1. Stoelting, R.K., "Pharmacokinetics and Pharmacodynamics of Injected and Inhaled Drugs", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 1-17.

2. Dolin, S. J. "Drugs and pharmacology" in Total Intravenous Anesthesia, pp. 13-35 (Nicholas L. Padfield, ed), Butterworth Heinemann, Oxford, 2000