enzyme induction

Enzyme induction is like hiring extra factory workers. When the body is exposed to certain drugs over time, it ramps up production of metabolizing enzymes, so the same drug — or another drug sharing that enzyme — gets broken down faster and faster.

Mechanistically, inducers (such as rifampicin, carbamazepine, phenytoin, and St John's wort) activate nuclear receptors like PXR and CAR, which increase transcription of cytochrome P450 genes. Because new protein must be synthesized, induction develops gradually over days to weeks and likewise wears off slowly after the inducer is stopped.

Clinically, induction tends to lower the blood levels and effect of co-administered drugs, risking therapeutic failure — a classic example is rifampicin reducing the effectiveness of oral contraceptives. Paradoxically, when the affected drug is a prodrug, induction can increase the amount of active drug formed, and faster metabolism of some drugs to reactive metabolites can heighten toxicity.