The simplest model allows for instantaneous distribution of drug throughout the blood (and probably to some extent tissues), but this is not then followed by any further slow movement elsewhere. This is shown in Figure 1. Drug spreads instantly throughout the blood and Tissues and 2, but never enters other tissues.


Figure 1: Basis of the one compartmental model.

The complete ADME process for the one compartmental situation is usually shown in schematic form as in Figure 2. Drug is injected or absorbed into the blood and distributes immediately throughout its range and is eventually eliminated.


Figure 2: Schematic diagram of drug handling with one compartment


Two compartment model

Figure 3 shows drug behaviour in a two compartment model. Drug is injected or absorbed and spreads instantly throughout the blood and the rapidly equilibrating tissues TI & T2 (First compartment) and then there is a significant delay while drug enters the rest of the body (Second compartment).


Figure 3: Basis of the two-compartmental model

There are two principal factors that can influence the rate at which drugs move in and out of tissues. The first is the polarity of the drug; non-polar drugs undergo pqssive diffusion easily and so can enter tissues more rapidly than polar ones. The other major factor is blood flow; where tissues have a rich blood supply, drugs can be delivered and removed quickly, whereas significant delay is unavoidable where blood flow is sparse. For many drugs, blood flow is the critical factor, and for the rest of this chapter, we will focus solely on that, but it should be remembered that polarity can be an issue and we will refer to this at a later point.


Table : Blood flow to a representative range of tissues.

Table shows a spectrum of blood flows measured in mL of blood per minute per gram of tissue. We tend to divide tissues into two broad categories — ‘Highly perfused’ and ‘Poorly perfused: For most drugs, the tissues shown as highly perfused will approximate the first compartment and the less well perfused ones, the second.

Notice that the two principal drug eliminating organs (Liver and kidney) are both well perfused and therefore form part of the first compartment. When we draw a schematic diagram of a two compartment system, we therefore indicate drug elimination as occurring only from the first compartment.