Non-specific Irreversible platelet cyclooxygenase inhibitor
(COX-1 and 2) via acetylation of serine residues → ↓formation PG precursors.
- Inhibits formation of thromboxane (TXA) → inhibit aggregation
- At higher doses prostacyclin (PFI2) synthesis also inhibited → vasoconstriction (but endothelium can regenerate COX)

Prodrug. Hepatic activation to active agent (Thiol derivative, by oxidation and hydrolysis) which is an ADP receptor antagonist
- Irreversible inhibition of P2Y12 receptor at platelet surface → Inhibits activation of GPIIb/IIIa → Inhibits platelet activation

Irreversibly binds the P2Y12-R (an ADP receptor), preventing activation of glycoprotein IIb/IIIa→ prevents platelet crosslinking

- PO. BA. 50%.
- 300mg Loading. 100mg maint.

- PO. BA 50%
- 600mg loading. 75mg maint.

85% protein binding, pKa 3

95% protein binding,

Vd 10L

Vd unknown

- Converted to salicylic acid in GI mucosa and liver
- Hepatic conjugation (saturable)

- Hepatic CYP450 2C19 + Esterases to Inactive metab

Prodrug- 1 step metabolism
Less susceptible to CYP polymorphism and CYP inhibition or induction than Clopidogrel

- Renal as salicylate

- Renal and faecal elimination

- T1/2b 15~20 mins when first order
- Dur: 4-6 hrs. (Effect on platelet aggregation will last life of current cohort of platelets (7-10 days)

- T1/2b 7 hours parent drug (30mins metab) Dur: life of platelet

Bleeding
Bronchospasm, Renal toxicity
Reye’s Syndrome, GI ulceration
Caution with other anticoagulants

Bleeding
TTP
Agranulocytosis, Neutropenia
Significant drug interactions as requires activation by CYP450

Antiplatelet

Antiplatelet

Antiplatelet

COX inhibitor

ADP Receptor Antagonist - Thienopyridine

ADP Receptor Antagonist - Thienopyridine

Prodrug

Level 1

Level 3

Level 3

Platelet inhibition

Platelet inhibition

Platelet inhibition