A patient on rifampicin for tuberculosis is also taking warfarin. His INR drops significantly, requiring a warfarin dose increase. This interaction is BEST explained by:

• A Rifampicin inhibits CYP2C9, reducing warfarin metabolism
• B Rifampicin is a potent PXR/CAR nuclear receptor activator inducing CYP3A4 and CYP2C9 transcription ✓
• C Rifampicin competes with warfarin for plasma protein binding
• D Rifampicin directly antagonizes vitamin K epoxide reductase

Explanation

Rifampicin is one of the most potent known inducers of xenobiotic-metabolizing enzymes. It activates PXR (pregnane X receptor) and CAR (constitutive androstane receptor) — nuclear receptors that, upon binding, translocate to the nucleus, heterodimerize with RXR, and drive transcription of CYP3A4, CYP2C9, CYP2C19, UGTs, and MDR1. Warfarin (S-enantiomer) is primarily metabolized by CYP2C9; increased CYP2C9 activity accelerates warfarin clearance, reducing INR. This is enzyme induction, not inhibition.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.