Two-Compartment Pharmacokinetic Model

Abstract

The two-compartment pharmacokinetic model describes the evolution of drug levels in the organism by depicting the body as two pharmacokinetic compartments (the central and the peripheral compartments, also commonly referred to as compartment 1 and compartment 2, in that order). Once a given drug amount reaches one of these compartments, it distributes throughout it immediately and homogenously. However, movement from one compartment to the other is not instantaneous but follows first-order kinetics. As in the onecompartment model, drug elimination occurs following (apparent) first-order kinetics. By default (i.e., unless otherwise specified), it is assumed that elimination occurs only from the central compartment. Depending on the modelled therapeutic scenario, drug absorption will be assumed to be instantaneous (e.g., intravenous bolus) or to follow zero- or first-order kinetics (e.g., constantrate intravenous infusion or extravascular drug administration, respectively). It is also assumed that the drug initially enters the central compartment, from which it distributes to the peripheral one. Two-compartment models are the most common in population pharmacokinetic modeling: it has been estimated that they represent around 80% of published models. By integrating the mass balances for each compartment, it is possible to obtain equations of drug amount in each compartment versus time.