What is the effect of enzyme induction on Clint, clearance, and exposure?

• A. Induction increases Clint, increasing Cl, reducing AUC and Css.
• B. Induction decreases Clint, decreasing Cl, increasing AUC.
• C. Induction has no effect on clearance or exposure.
• D. Induction decreases Css but increases AUC.

Answer: (A)

When enzymes are induced, the liver increases its metabolic capacity, raising intrinsic clearance (Clint). With Clint higher, hepatic clearance (Cl) goes up because more drug is removed per unit time, especially when Clint is not already limited by blood flow. For a given dose delivered IV, exposure is inversely related to clearance: AUC = Dose/Cl, so as clearance rises, AUC falls. Likewise, at a constant dosing rate (as in a steady IV infusion), steady-state concentration Css = Rate_in / Cl; higher clearance leads to a lower Css. Therefore, enzyme induction raises Clint, increases clearance, and reduces both exposure (AUC) and steady-state concentration (Css).