Compartment modelsA mathematic representation of the body or an area of the body created to study physiologic or pharmacologic kinetic characteristics. A compartment model can simulate all of the biologic processes involved in the kinetic behavior of a drug after it has been introduced into the body, leading to a better understanding of its pharmacodynamic effects. Studies most frequently use one- or two-compartment models. In a one-compartment model the body assumes the characteristics of a homogeneous unit in which an administered drug diffuses instantaneously in the volume of body fluid. In a two-compartment model the body is represented as two distinct compartments, a central and a peripheral compartment, with two separate fluid volumes. Compartment models can be used to model the transport processes between interconnected volumes, such as the flow of drugs and hormones in the human body. Compartment models assume that there is perfect mixing so that the drug concentration is constant in each compartment. The complex transport processes are approximated by assuming that the flow rates between the compartments are proportional to the concentration differences in the compartments. One of the early uses of compartment modes was by Widmark in the 1920s, who modeled the propagation of alcohol in the body. Compartment models are now important for the screening of all drugs used by humans.

Drug Transport processes involved in drug transport

One, Two and Three Compartment ModelsFortunately many of the processes involved in drug movement around the body are not saturated at normal therapeutic dose levels. The pharmacokinetic - mathematical models that can be used to describe plasma concentration as a function of time can then be much simplified. The body may even be represented as a single compartment or container for some drugs. For other drugs a two or three compartment model is found to be necessary.

Intravenous Bolus one compartment

Figure below shows the body before and after a rapid IV bolus injection, considering the body to behave as a single compartment. In order to simplify the mathematics it is often possible to assume that a drug given by rapid intravenous injection, a bolus, is rapidly mixed. This figure represents the uniformly mixed drug very shortly after administration.

Intravenous Bolus Two Compartment Model

An intravenous bolus injection with a two compartment model. Often a one compartment model is not sufficient to represent the pharmacokinetics of a drug. A two compartment model often has wider application. Here we consider the body is a central compartment with rapid mixing and a peripheral compartment with slower distribution. The central compartment is uniformly mixed very shortly after drug administration, whereas it takes some time for the peripheral compartment to reach pseudo equilibrium.

Three compartment model

The three-compartment model is an extension of the two-compartment model, with an additional deep tissue compartment. A drug that demonstrates the necessity of a three-compartment open model is distributed most rapidly to a highly perfused central compartment, less rapidly to the second or tissue compartment, and very slowly to the third or deep tissue compartment, containing such poorly perfused tissue as bone and fat. The deep tissue compartment may also represent tightly bound drug in the tissues.

Importance of compartment models:

In hypothetical estimation of in vivo release of drugs.

Doses: for example from the high concentrations typically used in laboratory experiments to those found in the environment so used in dose calculation.

Exposure duration: e.g., from continuous to discontinuous, or single to multiple exposures (single dosing to multiple dosing)

Routes of administration: e.g., from inhalation exposures to ingestion (oral).

Species: e.g., transpositions from rodents to human, prior to giving a drug for the first time to subjects of a clinical trial, or when experiments on humans are deemed unethical, such as when the compound is toxic without therapeutic benefit

Individuals: e.g., from males to females, from adults to children, from non-pregnant women to pregnant.