Compartmental Model

A compartmental model treats the body as a small number of imaginary tanks. The central compartment holds plasma and the tissues that equilibrate with it almost instantly; peripheral compartments hold tissue that fills and empties more slowly, connected by transfer rate constants. Elimination normally happens only from the central compartment. Fit a curve with two compartments and the log-concentration plot breaks into two straight segments: a steep distribution phase as drug moves outward, then a shallower terminal phase reflecting elimination and slow return from tissue.

The compartments correspond to nothing anatomical, which is the point most often missed. They are the smallest number of exponentials that describe the data. Peptides given intravenously commonly need two, since growth hormone and insulin both show a rapid initial fall followed by a slower tail, and population models for long-acting injected analogues typically pair a two-compartment disposition with first-order absorption. How many compartments a drug appears to have is partly a property of the sampling schedule: sample sparsely and everything looks like one compartment.

The model determines which half-life is worth quoting. In a two-compartment drug, the terminal phase may carry only a small share of total exposure, so the headline half-life can be almost irrelevant to accumulation.

The trap is quoting the terminal number as though it described the whole drug. A long tail at concentrations far below anything pharmacologically active tells you about assay sensitivity and slow tissue release, not about duration of effect. Improve the assay and the terminal half-life lengthens while nothing about the drug has changed, which is why an effective half-life derived from observed accumulation is usually the more honest figure.