Three compartment drug

A three-compartment drug is one, such as propofol, that distributes very rapidly into tissues that are part of the central compartment, distributes at a moderate rate into tissues that make up the shallow tissue compartment, and distributes slowly into tissues that make up the deep tissue compartment. Analysis of graphed data requires software-based approaches. Pharmaceutical companies typically use physiological modelling to determine or predict PK parameters for drugs (including one and two-compartment drugs), as multi-compartment behaviour is common, and compartment-based approaches quickly become too cumbersome when three or more compartments are discernible. Physiological modelling is a software-based approach that considers blood flow and tissue composition characteristics of all major tissues and organ systems to predict the overall rates and extents of absorption, distribution and elimination.

Propofol is an example of a drug that has a clinically-important context-sensitive half-time. This phenomenon refers to the impact of ceasing drug administration prior to reaching equilibration between the central compartment and one or more tissue compartments. Drug concentration in the central compartment falls most slowly on terminating administration when drug has equilibrated fully between compartments, while rate of drug loss from the central compartment is faster if administration is terminated prior to that point. This is true for any drug behaving with two- or multi-compartment kinetics, but the effect only becomes clinically important when the target organ for the drug is part of the central compartment (or is part of any compartment that is not the outermost (or deepest) compartment.