Understanding Compartment Models for Drug Transport
1. Compartment models
A 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.
2. Drug Transport processes involved in drug transport
One, Two and Three Compartment Models
Fortunately 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.
3. 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.
4.
5. 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.