Relationship Between Concentration and Effect
The intensity and total duration of any pharmacological effect are directly dependent on the concentration achieved in target organs. The physician's main therapeutic goal is always to maintain a strictly defined drug level in tissues.
However, a significant practical challenge arises: directly measuring the amount of a substance in a specific organ in a living patient is virtually impossible. The solution is regular sampling from the bloodstream. Measuring the active substance level in blood plasma provides an objective picture because there is a clear correlation between how much drug circulates in the bloodstream and how much has accumulated in target organs.
The Pharmacokinetic Curve
The plasma drug level is never static. It is continuously influenced by four fundamental processes:
- Absorption — entry from the site of administration.
- Distribution — transport across organs and tissues.
- Storage (Deposition) — temporary accumulation in body structures.
- Elimination — removal of the substance from the body, combining biotransformation (metabolism) and excretion.
To quantitatively assess these stages, a pharmacokinetic curve is plotted — a graphical representation of how plasma concentration changes over time. The shape of the graph heavily depends on the route of administration. If given intravenously (as a bolus), the substance enters instantly, the curve starts at the maximum point ($C_0$), and immediately enters the elimination phase. For extravascular routes (e.g., per os administration), the curve starts at zero, has a prominent absorption phase, reaches a peak, and only then declines.
One-Compartment Model
For mathematical calculations, the human body is conventionally represented as a system of reservoirs (compartments). The simplest option is the one-compartment pharmacokinetic model. In this model, the entire body is viewed as a single compartment completely filled with fluid.
The core postulate of this concept states that following administration, the drug distributes throughout the entire volume instantaneously and completely uniformly. The key parameters here are the administered dose (denoted as D) and the initial concentration of the substance immediately after complete distribution (denoted as $C_0$). Drug loss from this single compartment occurs exclusively via elimination processes.
Two-Compartment Model and Kinetics Phases
To more accurately describe drug behavior (especially after intravenous administration), a two-compartment pharmacokinetic model is used. In this case, the body is divided into two communicating sectors:
- Central compartment — includes the blood itself and well-perfused organs. The drug initially enters here, and elimination also occurs from this sector.
- Peripheral compartment — poorly perfused tissues, into which the substance slowly distributes from the central sector.
Continuous redistribution occurs between the compartments. The concentration graph in such a model is biphasic, forming a biexponential curve. It clearly shows a steep initial drop (the $\alpha$-phase, reflecting distribution) and a long shallow "tail" (the $\beta$-phase, indicating elimination). In a simplified version (monoexponential curve), the logarithm of concentration decreases linearly, which allows graphical determination of the half-life.