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The compartmental concepts in pharmacokinetics are used to ensure accurate estimation of pharmacokinetic parameters, such as elimination half‐life, the volume of distribution and elimination rate constant of a drug. The knowledge and understanding of compartmental concepts enable fitting of the pharmacokinetic profile into appropriate models to ensure the dosage regimens are predicted correctly in clinical settings.

The compartmental behaviour of a drug strongly depends on its distribution characteristics in the body and how quickly a drug achieves a distribution equilibrium. Many drugs follow a simple one‐compartmental model, where the whole body is treated as one single compartment and the distribution equilibrium is achieved instantaneously, see Figure 2.12. Achieving distribution equilibrium implies that the rate of transfer of drug from the blood to all body tissues and the rate of drug transfer from the body tissues back to the blood become equal instantaneously.

For some drugs, the distribution equilibrium takes time (several minutes to hours) depending upon the physicochemical properties of the drug. Often, the distribution of these drugs to the body tissues is very slow and the drug is distributed to highly perfused organs first, such as brain, heart, lung, liver and kidneys, which together with systemic circulation forms the first or the central compartment. The drug distribution to other tissues, such as muscles, bones and adipose tissues, is slower. These tissues can be grouped and referred to as the second compartment, also known as peripheral or the tissue compartment. For such drugs, the distribution equilibrium between the two compartments can take several minutes to hours to establish. Therefore, it requires the fitting of plasma concentration–time profile data into appropriate models for accurate estimation of pharmacokinetic parameters that could enable clinically relevant predictions of the dosage regimens. This is shown in Figure 2.13.

Advanced in silico tools that can also predict drug absorption, metabolism, distribution and elimination in the body using inputs on physicochemical properties and ADME parameters and they are described in detail in Chapter 12.

Figure 2.12 One‐compartmental pharmacokinetic model, distribution equilibrium is achieved instantaneously.

Figure 2.13 Two‐compartmental pharmacokinetic model, distribution equilibrium is slow and takes time.