How can you determine if a drug follows linear pharmacokinetics?

• A. If increasing dose leads to non-proportional changes in AUC.
• B. If increasing dose results in proportional increases in AUC and Cmax and CL/Vd remain constant across doses.
• C. If clearance decreases with dose.
• D. If half-life changes with dose.

Answer: (B)

Linear pharmacokinetics means the body's handling of the drug is not saturated as the dose changes. In this situation, the exposure and the peak levels rise directly in proportion to the dose, and the elimination and distribution parameters stay the same across doses. Specifically, AUC, which represents overall exposure, increases in direct proportion to the dose when clearance remains constant (AUC = Dose/Cl). Similarly, Cmax tends to scale with the dose under the same conditions because the amount of drug entering the system and the rate of elimination are not changing in a saturable way. With constant clearance and volume of distribution, the half-life remains the same regardless of dose since t1/2 = 0.693 × Vd/Cl. If you observed the clearance changing with dose or a changing half-life, that would indicate nonlinear pharmacokinetics due to saturation or other dose-dependent processes. Therefore, proportional increases in AUC and Cmax with dose and constant CL/Vd across doses are the telltale signs of linear pharmacokinetics.