Pharmacokinetic modelling is performed by non-compartmental or compartmental methods. Non-compartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Non-compartmental methods are often more versatile in that they do not assume any specific compartmental model and produce accurate results also acceptable for bioequivalence studies.

These models are based on a consideration of an organism as a number of related compartments. The simplest idea is to think of an organism as only one homogenous compartment. This mono compartmental model presupposes that blood plasma concentrations of the drug are a true reflection of the drug's concentration in other fluids or tissues and that the elimination of the drug is directly proportional to the drug's concentration in the organism (first order kinetics).

If these relative conditions for the different tissue types are considered along with the rate of elimination, the organism can be considered to be acting like two compartments: one that we can call the central compartment that has a more rapid distribution, comprising organs and systems with a well-developed blood supply; and a peripheral compartment made up of organs with a lower blood flow. Other tissues, such as the brain, can occupy a variable position depending on a drug's ability to cross the barrier that separates the organ from the blood supply.

This model may not be applicable in situations where some of the enzymes responsible for metabolizing the drug become saturated, or where an active elimination mechanism is present that is independent of the drug's plasma concentration. In the real world each tissue will have its own distribution characteristics and none of them will be strictly linear.

Due to the dependence on the length of x in the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the closer time points are, the closer the trapezoids reflect the actual shape of the concentration-time curve. The number of time points available in order to perform a successful NCA analysis should be enough to cover the absorption, distribution and elimination phase to accurately characterize the drug.

The advantage of compartmental over some non-compartmental analyses is the ability to predict the concentration at any time. The disadvantage is the difficulty in developing and validating the proper model. For drugs to be effective they need to be able to move rapidly from blood plasma to other body fluids and tissues.

Regards
Rutherford
Managing Editor
Journal of Pharmacy Practice and Education