In a two-compartment model, how do the central and peripheral compartments differ?

• A. The central compartment contains poorly perfused tissues; the peripheral compartment contains blood.
• B. The central compartment contains blood and highly perfused organs; the peripheral compartment represents less-perfused tissues where the drug slowly exchanges.
• C. The central compartment is only the plasma; the peripheral is the extracellular fluid.
• D. The central and peripheral compartments exchange at a rate constant k12 only.

Answer: (B)

In a two-compartment model, the central compartment represents blood and highly perfused organs, where drug concentrations change quickly after administration, while the peripheral compartment stands for less-perfused tissues where distribution occurs more slowly. After dosing, the drug rapidly equilibrates within the central compartment and then gradually distributes to the peripheral compartment. Movement between the two compartments is bidirectional and governed by two rate constants: k12 from central to peripheral and k21 from peripheral back to central. This framework captures why the central area is a fast-responding hub (blood and well-perfused tissues) and the peripheral area is a slower-exchanging tissue group. The other descriptions misstate either which tissues are in each compartment or the nature of exchange (it is not unidirectional nor limited to a single rate constant).