Distribution and elimination phases

Anatomical structure of compartments in pharmacokinetics

To understand how a drug behaves inside the body, pharmacologists use special models. The most popular one divides all organs and tissues into two large groups, or "compartments", depending on how intensively they are supplied with blood.

1. Central compartment. It includes blood plasma itself, as well as organs through which the maximum blood flow passes. These traditionally include the heart (cor), liver (hepar), kidneys (renes), and lungs (pulmones). The main characteristic of this compartment is that any drug distributes here almost instantaneously. As soon as the drug enters the systemic circulation, it immediately and completely uniformly fills the entire volume of the central pool.
2. Peripheral compartment. It includes tissues with less intensive blood supply. These include the skin (cutis), adipose tissue, and muscle tissue (musculi). Unlike the central pool, the drug penetrates these anatomical structures not immediately, but gradually.

$\alpha$-phase (Distribution phase)

After administration, any drug begins its movement. The first stage of this movement is called the $\alpha$-phase, or the distribution phase.

The direction of molecular transport at this stage is strictly defined: the substance actively moves from the central compartment into the peripheral one. Looking at the plasma drug concentration-time curve, we see a very rapid and sharp drop. It is important to understand that this drop occurs not because the drug has left the body, but solely due to the substance moving from plasma into tissues with lower blood supply.

This process is described by a special pharmacokinetic parameter — the half-distribution period, denoted as $t_{1/2}\alpha$. A key feature of this phase is its high rate. Distribution always proceeds significantly faster than the subsequent elimination of the drug. Mathematically, this is expressed by the strict inequality: $t_{1/2}\alpha < t_{1/2}\beta$.

$\beta$-phase (Elimination phase)

Once the tissues of the peripheral compartment are saturated with the drug, the second stage begins — the $\beta$-phase, also called the elimination phase.

Now the direction of transport radically changes. The drug begins its reverse movement: it shifts from the peripheral compartment back to the central one, and from there its final removal from the body takes place.

The process of plasma drug concentration decrease at this stage is very slow. This phase reflects the true elimination (clearance) of the xenobiotic from the body. The main parameter here is the elimination half-life, denoted as $t_{1/2}\beta$. It is worth noting an important practical detail: when you open a medical reference book and see the $t_{1/2}$ parameter, in the vast majority of cases it refers specifically to the elimination half-life, not the distribution half-life.

Elimination rate constant ($k_{el}$)

To quantitatively describe the process of drug removal, pharmacology uses the elimination rate constant, or $k_{el}$.

Its physical meaning is very specific: it shows exactly what fraction of the substance is removed from the body per unit of time. The dimension of this indicator is expressed in reciprocal time — for example, in minutes to the minus first power ($min^{-1}$) or hours to the minus first power ($h^{-1}$).

Calculation example: Suppose that for a certain drug, the elimination rate constant $k_{el}$ is $0.1\text{ h}^{-1}$. In practical terms, this means that in exactly one hour, 10% of the amount of the substance present in the body at the beginning of that hour will be eliminated.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Anatomical features of central compartment organs
• Mechanisms of gradual substance penetration into peripheral compartment tissues
• Clinical significance of the half-distribution period ($t_{1/2}\alpha$)
• Mathematical calculation of the elimination rate constant ($k_{el}$)
• Comparison of the rates of $\alpha$ and $\beta$ phases

Other topics in "General Pharmacology"

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