Which cytochrome P450 isoenzyme metabolizes warfarin most significantly?

• A. CYP2C9
• B. CYP3A4
• C. CYP1A2
• D. CYP2D6

Answer: (A)

CYP2C9 is the main enzyme responsible for warfarin clearance, especially for the more potent S-enantiomer. Because this isoenzyme handles the majority of warfarin metabolism, it largely determines how long the drug stays active in the body and how strong its anticoagulant effect will be. Genetic variants that slow CYP2C9 activity or drugs that inhibit it can raise warfarin levels and bleeding risk, while factors that speed it up tend to reduce the drug’s effect.

Other enzymes do contribute—CYP3A4 and CYP1A2 help metabolize the other enantiomer and play smaller roles in overall clearance—but their impact on warfarin’s anticoagulant strength is not as significant as that of CYP2C9.