In a two-compartment PK model, what do the α and β rate constants represent?

• A. α is the distribution rate constant between central and peripheral compartments; β is the elimination rate constant governing overall drug loss.
• B. α is the absorption rate constant; β is the distribution rate constant between compartments.
• C. α is the elimination rate constant; β is the distribution rate constant.
• D. α and β are both elimination rate constants.

Answer: (A)

In a two-compartment model after an IV bolus, the concentration-time profile shows two phases: a rapid distribution phase and a slower elimination phase. The distribution rate constant, α, describes the fast exchange of drug between the central (blood) and peripheral (tissue) compartments during the initial drop in plasma concentration. The terminal rate constant, β, describes the slower, final decline of drug concentration as elimination processes govern overall drug loss from the body, with redistribution still contributing but not dominating the slope. Since absorption is not involved with IV administration, α is not an absorption rate, and β represents the elimination-dominated terminal phase rather than a pure distribution rate. Thus α corresponds to distribution between compartments, and β corresponds to the elimination (terminal) decline.