In a tuberculosis patient treated with rifampicin, the plasma levels of warfarin fall dramatically within a week of starting anti-TB treatment. What is the mechanism?
- A Rifampicin is a potent inducer of CYP2C9, CYP3A4, P-glycoprotein, and hepatic glucuronosyltransferases, dramatically increasing warfarin clearance ✓
- B Rifampicin inhibits CYP2C9, reducing warfarin metabolism and paradoxically raising free levels
- C Rifampicin competitively displaces warfarin from albumin binding sites, increasing its volume of distribution
- D Rifampicin chelates vitamin K in the gut, reducing hepatic synthesis of clotting factors
Correct answer: A. Rifampicin is a potent inducer of CYP2C9, CYP3A4, P-glycoprotein, and hepatic glucuronosyltransferases, dramatically increasing warfarin clearance
Explanation
Rifampicin is the most potent known inducer of hepatic CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP2D6), as well as P-glycoprotein, glucuronosyltransferases, and sulfotransferases, through activation of the pregnane X receptor (PXR) and constitutive androstane receptor (CAR). This dramatically increases warfarin (and many other drugs') clearance; INR drops within days and warfarin dose often needs to be 3–5 times the usual dose while rifampicin is co-administered.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.