      Section 1 - Pharmacokinetic Concepts

### Distribution

Distribution is the process by which a drug diffuses or is transferred from intravascular space to extravascular space (body tissues). These spaces are described mathematically as volume(s) of distribution.

In the simplest of terms, a drug's volume of distribution is that volume of bodily fluid into which a drug dose is dissolved. Therefore, if we know the dose that was given, and we can measure the serum level (concentration), then we can calculate a volume:

Volume of distribution = Dose / drug concentration

Of course, the human body is not a glass beaker. Drug is distributing in and out of many tissue compartments while it is simultaneously being eliminated. This complex and continually changing environment must be simplified in order to mathematically model the human body. Therefore, the body is usually divided into two spaces, a central and a tissue compartment.

Central volume (Vc)
The central volume of distribution (Vc) is a hypothetical volume into which a drug initially distributes upon administration. This compartment can be thought of as the blood in vessels and tissues which are highly perfused by blood. Central volume of distribution (Vc) may be calculated as:

Vc = Dose / Peak serum level
Note: by rearranging this equation we can see that dose and Vc are the primary determinates of the peak level:
Peak = Dose / Vc

Peripheral volume (Vt)
The peripheral volume is the sum of all tissue spaces outside the central compartment. Of course, all peripheral tissues are not homogenous, this is a simplification for the purpose of creating a usable mathematical model.

All drugs initially distribute into the smaller Vc before distributing into the peripheral volume. Together, Vc and Vt create the apparent volume of distribution (Vd). Apparent volume of distribution (Vd)
Apparent Vd is a term used to describe the volume of fluid that would be required to account for all drug in the body. It does not necessarily refer to any identifiable compartment in the body. It is simply the size of a compartment necessary to account for the amount of drug in the body. Because Vd is hypothetical in nature, it is referred to as an apparent volume.

As you will see, distribution volumes are important for estimating:

• Amount of drug in the body
• Peak serum levels
• Clearance

Summary
To review, the most commonly used volumes of distribution are:

• Central volume (Vc)
• Tissue (or peripheral) volume (Vt)
• Apparent volume of distribution (Vd)      Section 1 - Pharmacokinetic Concepts