A 64-year-old man receiving clopidogrel after coronary stenting is prescribed omeprazole for dyspepsia. His cardiologist switches him to pantoprazole. What pharmacological reason justifies this change?
- A Omeprazole induces CYP3A4, accelerating clopidogrel clearance
- B Omeprazole inhibits CYP2C19, reducing conversion of clopidogrel to its active metabolite ✓
- C Pantoprazole enhances absorption of clopidogrel from the gut
- D Omeprazole displaces clopidogrel from plasma protein binding sites
Correct answer: B. Omeprazole inhibits CYP2C19, reducing conversion of clopidogrel to its active metabolite
Explanation
Clopidogrel is a prodrug requiring CYP2C19 mediated oxidation to its active thiol metabolite. Omeprazole competitively inhibits CYP2C19 and attenuates platelet inhibition, although the clinical significance of this interaction is debated in guidelines. Pantoprazole has much weaker CYP2C19 inhibition, making it the preferred proton pump inhibitor with clopidogrel. Induction, absorption enhancement and protein binding displacement are not involved in this well known interaction.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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