Clopidogrel is a prodrug requiring biotransformation to its active metabolite. Which enzyme system converts clopidogrel to its active thiol metabolite?

• A CYP2C19 ✓
• B CYP2D6
• C CYP3A4 alone
• D Paraoxonase-1 (PON1) in the liver

Explanation

Clopidogrel undergoes two-step hepatic activation primarily via CYP2C19 (with some contribution from CYP3A4) to form the active thiol metabolite that irreversibly inhibits the P2Y12 ADP receptor on platelets. CYP2C19 loss-of-function polymorphisms (e.g., *2 allele, common in Asian populations) lead to reduced active metabolite formation and inadequate platelet inhibition. Proton pump inhibitors (especially omeprazole) inhibit CYP2C19 and reduce clopidogrel efficacy; pantoprazole has less interaction.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.