Rifampicin is a potent inducer of hepatic CYP enzymes. Compared to enzyme inhibition, which statement about enzyme induction is correct?

• A Enzyme induction decreases clearance of co-administered substrates, leading to toxicity
• B Enzyme induction reduces the volume of distribution of the affected drug
• C Enzyme induction increases enzyme synthesis, and its clinical effect takes days to weeks to manifest ✓
• D Enzyme induction increases protein binding of the co-administered drug, raising free fraction

Explanation

Enzyme induction increases the synthesis of CYP enzymes (via nuclear receptors such as PXR), so the maximal effect requires days to weeks as new enzyme is produced. This decreases plasma concentrations of co-administered substrates, potentially reducing efficacy (not toxicity). It does not affect volume of distribution or protein binding. Rifampicin, carbamazepine, and phenytoin are classic inducers.

Reference: Katzung and Trevor's Pharmacology: Examination and Board Review, 13th ed.

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