Two-Compartment Open Model

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Chapter: Biopharmaceutics and Pharmacokinetics : Compartment Modelling

The commonest of all multicompartment models is a two-compartment model.


The commonest of all multicompartment models is a two-compartment model. In such a model, the body tissues are broadly classified into 2 categories –

1. Central Compartment or Compartment 1 comprising of blood and highly perfused tissues like liver, lungs, kidneys, etc. that equilibrate with the drug rapidly. Elimination usually occurs from this compartment.

2. Peripheral or Tissue Compartment or Compartment 2 comprising of poorly perfused and slow equilibrating tissues such as muscles, skin, adipose, etc. and considered as a hybrid of several functional physiologic units.

Classification of a particular tissue, for example brain, into central or peripheral compartment depends upon the physicochemical properties of the drug. A highly lipophilic drug can cross the BBB and brain would then be included in the central compartment. In contrast, a polar drug cannot penetrate the BBB and brain in this case will be a part of peripheral compartment despite the fact that it is a highly perfused organ.

The plasma concentration for a drug that follows a two-compartment model declines biexponentially as the sum of two first-order processes – distribution and elimination.

Depending upon the compartment from which the drug is eliminated, the two-compartment model can be categorized into 3 types:

1. Two-compartment model with elimination from central compartment.

2. Two-compartment model with elimination from peripheral compartment.

3. Two-compartment model with elimination from both the compartments.

In the absence of information, elimination is assumed to occur exclusively from central compartment.

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