A 62-year-old man with an acute coronary syndrome receives clopidogrel and shows minimal platelet inhibition on testing. Genotyping reveals he is a poor metaboliser at the relevant enzyme locus. Which enzyme is required to convert clopidogrel into its active thiol metabolite?
- A CYP2C19 ✓
- B UGT1A1
- C NAT2
- D Glutathione S-transferase
Correct answer: A. CYP2C19
Explanation
Clopidogrel is a prodrug that needs two sequential CYP-mediated oxidative steps, chiefly by CYP2A19, to generate the active thiol metabolite that irreversibly blocks the platelet P2Y12 receptor. Poor CYP2A19 metabolisers get reduced antiplatelet effect, unlike paracetamol where CYP2E1 creates a toxic product. NAT2 handles isoniazid acetylation and UGT1C1 glucuronidates bilirubin and irinotecan, not clopidogrel activation.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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