Which of the following drug pairs demonstrates a pharmacokinetic interaction through competitive inhibition of the same cytochrome P450 enzyme?

Explanation

## Pharmacokinetic Drug Interactions via CYP450 Inhibition **Key Point:** Warfarin and fluconazole interact through competitive inhibition of CYP2C9, the primary enzyme responsible for warfarin metabolism. This inhibition decreases warfarin clearance, increasing its plasma concentration and anticoagulant effect, raising the risk of bleeding. ### Mechanism of Interaction Fluconazole is a potent inhibitor of CYP2C9. When co-administered with warfarin: 1. Fluconazole competitively binds to CYP2C9 active site 2. Warfarin metabolism is impaired 3. Warfarin accumulates → increased INR → bleeding risk **High-Yield:** Common CYP2C9 inhibitors include fluconazole, miconazole, NSAIDs, and amiodarone. All increase warfarin effect. ### Comparison with Other Interactions | Interaction Pair | Mechanism | Type | | --- | --- | --- | | Warfarin + fluconazole | CYP2C9 inhibition | Pharmacokinetic | | Warfarin + aspirin | Platelet inhibition + displacement | Pharmacodynamic | | Metformin + contrast dye | Renal impairment → lactic acidosis | Pharmacodynamic | | Digoxin + loop diuretics | Hypokalemia → toxicity | Pharmacodynamic | **Clinical Pearl:** Warfarin-fluconazole interaction is clinically significant and requires INR monitoring and possible warfarin dose reduction. **Mnemonic:** **CYP2C9 Warfarin Inhibitors = FIMAN** - **F**luconazole - **I**soniazid (weak) - **M**iconazole - **A**miodarone - **N**SAIDs