Which statement correctly describes linear pharmacokinetics?

• A. If dose increases, AUC and Cmax increase proportionally and CL/Vd remain constant across doses.
• B. AUC increases more than proportionally.
• C. CL decreases with dose.
• D. Vd increases with dose.

Answer: (A)

Linear pharmacokinetics means the body's handling of the drug is proportional to the dose across the tested range, with clearance and volume of distribution effectively constant. When clearance is constant, total exposure, reflected by AUC, changes in direct proportion to the dose (AUC ≈ Dose/CL, or F×Dose/CL for non‑IV). Similarly, peak concentration (Cmax) tends to rise in direct proportion to the dose when absorption and distribution aren’t saturating. Because the same clearance and volume of distribution apply at different doses, their relationship stays constant, so the system behaves predictably and proportionally as dose changes. Deviations from this—such as AUC increasing more than proportionally, or clearance or volume changing with dose (e.g., saturable metabolism)—are signs of nonlinear pharmacokinetics.