Volume of Distribution

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*Volume of Distribution (from Loading Dose)*

Overview

We rearrange the formula for loading dose to generate a formula for volume of distribution.

Equation

Starting with the loading dose formula:

Loading dose = (VdTC)/F

We rearrange to achieve the Volume of Distribution (Vd) as follows:

Meaning of Equation

Volume of distribution is the total amount of drug in systemic circulation divided by the plasma drug concentration.
It conceptualizes the volume of tissue that a drug will spread out into in order to maintain the plasma concentration at a particular level: the more widely the drug distributes, the greater the volume of distribution, and the larger the amount of drug necessary to keep it at a particular plasma concentration.

Note that the concentration variable (C) does not have to refer to plasma but can technically represent any compartment: for instance, whole blood (Cb), plasma (Cp), aqueous environment (water) (Ca). The concentration variable is called the central (or reference compartment): the volume of distribution is determined in reference to that compartment. We often see the C variable used synonymously with plasma concentration because that is the most common use of the equation.
Also, note that this volumetric measurement is a theoretical volume that is irrespective of actual body size; if it’s hard to keep a drug in the plasma, then this volume could exceed that of an average human being. In that case, it would be apparent that it’s just not possible to achieve the plasma concentration of drug desired without some other influence on the drug, keeping it in the plasma.

Example

As an example, we can calculate that:

Compartment Illustration

It helps to visualize Volume of Distribution as two compartments, which we can represent with boxes: Plasma and Tissues. The units of drug distribute into each compartment in a consistent ratio.
Indicate that the following variables INCREASE Vd: