Skip to main content
. Author manuscript; available in PMC: 2022 Mar 1.
Published in final edited form as: Nat Rev Cardiol. 2021 May 5;18(9):649–665. doi: 10.1038/s41569-021-00549-w

Fig. 2 |. Clopidogrel metabolism.

Fig. 2 |

Clopidogrel is administered as a prodrug. Approximately 85% of the prodrug is hydrolysed by carboxyl esterase 1 (CES1) to an inactive carboxylic acid derivative. The remaining drug undergoes metabolism to the oxo-clopidogrel intermediate metabolite, which is then metabolized to either the active thiol metabolite or to an inactive endo thiol metabolite via paraoxonase 1 (PON1). The active thiol metabolite inhibits platelet activation through irreversible binding to the platelet P2Y purinoceptor 12 (P2Y12 receptor). Multiple cytochrome P450 (CYP) enzymes are involved in the two-step bioactivation process21. CYP2C19 is involved in both steps of the process and is essential for clopidogrel activation.