Volume of Distribution in Pharmacokinetics

Volume of Distribution

• Warfarin has a small volume of distribution due to high binding to serum albumin, resulting in a small free fraction of drug in the blood (fB).
• Digoxin has a large volume of distribution because it is highly bound to tissues (primarily muscle), resulting in a small free fraction of drug in the tissues (fT).

Factors Affecting Volume of Distribution

• The volume of distribution (V) is determined by the actual volume of blood (VB) and the size of various tissues and organs of the body (VT).
• Body size affects volume of distribution; a larger person would have a larger volume of distribution for a drug.
• The binding of a drug in the blood or serum compared to its binding in tissues is an important determinant of the volume of distribution.

Drug Interactions and Volume of Distribution

• When a drug that is highly bound to plasma proteins is given concurrently with a second drug that is also highly bound to the same plasma protein, the second drug competes for plasma protein binding sites, displacing the first drug and increasing its free fraction in the serum (fB).
• This leads to an increased volume of distribution.

Elimination and Half-Life

• Serum concentrations of a drug decline in a curvilinear fashion, but decrease in a linear fashion on a semilogarithmic axis during the elimination phase.
• The time it takes for serum concentrations to decrease by half in the elimination phase is the half-life (t1/2), which is a constant and has the dimension of time.

Loading Dose and Steady State Concentration

• The loading dose (LD) required to achieve a particular steady-state drug concentration is determined by the volume of distribution (V): LD = Css V.