|
| | Clopidogrel [8] | Ticagrelor [9] | Prasugrel [10] |
|
| Class | Thienopyridine | Nucleoside analogue | Thienopyridine |
| Prodrug | Yes | No | Yes |
| Route | Oral | Oral | Oral |
| Metabolism | Hepatic | Hepatic (CYP34A) | Intestinal, serum, hepatic |
| Mechanism of action | Active metabolite IRREVERSIBLY inhibits P2Y12 subtype of ADP receptors on the platelet surface, which prevents activation of GIIb/IIIa receptor complex, thereby reducing platelet activation and aggregation; platelets blocked by clopidogrel are affected for the remainder of their lifespan (~7–10 days); note that genetic variability of CYP2C19 may preclude patients from the full effect of drug | REVERSIBLY and noncompetitively binds the P2Y12 subtype of ADP receptors on the platelet surface, which prevents ADP-mediated activation of the GIIb/IIIa receptor complex, thereby reducing platelet aggregation; due to reversible antagonism of the P2Y12 receptor, recovery of platelet function is likely to depend on serum concentrations of drug and its active metabolite | Active metabolite IRREVERSIBLY blocks the P2Y12 subtype of ADP receptors on the platelet, which prevents activation of the GIIb/IIIa receptor complex, thereby reducing platelet activation and aggregation; platelet aggregation returns to baseline within 5–9 days of discontinuation |
| Onset of action (IPA) | 300–600 mg loading dose detected within 2 hours | 180 mg loading dose ~41% within 30 minutes | 60 mg loading dose within 30 minutes |
| Time to maximal IPA | 6 hours after loading dose | 4–8 hours after loading dose | 4–8 hours after loading dose |
| Half-life elimination of active metabolite | ~30 minutes | ~9 hours | ~7 hours (range 2–15 hours) |
| Excretion | Renal (50%), biliary (46%) | Biliary | Renal (~68%), biliary (~27%) |
| Significant adverse effects | None | Increased minor/major bleeding | Increased minor/major bleeding |
| Contraindications | Hypersensitivity, active bleeding, significant liver impairment, and cholestatic jaundice | Hypersensitivity, active bleeding, history of intracranial hemorrhage, hepatic impairment, concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, atazanavir, nefazodone) | Hypersensitivity, active bleeding, history of TIA, or stroke |
|
