How do enzyme induction and inhibition affect PK?

• A. Induction decreases clearance; inhibition increases clearance.
• B. Induction increases clearance; inhibition decreases clearance.
• C. Induction and inhibition have no effect on clearance.
• D. Induction increases half-life; inhibition has no effect.

Answer: (B)

Metabolic enzyme activity determines how fast a drug is eliminated, so changes in enzyme levels or activity directly affect clearance and, in turn, the half-life and exposure. When enzymes are induced, more enzyme is available to metabolize the drug, increasing clearance and usually reducing exposure (lower AUC) and shortening the half-life (t1/2 tends to drop since t1/2 = 0.693 × Vd / CL). When enzymes are inhibited, metabolism slows, decreasing clearance, increasing exposure, and lengthening the half-life. Therefore, the statement that induction increases clearance and inhibition decreases clearance captures these directional effects. Induction generally takes time to develop because it requires increased enzyme synthesis, while inhibition can be immediate or rapid depending on the mechanism.