Mechanism of action<unk>  is a member of the thienopyridine class of ADP receptor inhibitors, like ticlopidine (trade name Ticlid) and clopidogrel (trade name Plavix). These agents reduce the aggregation ("clumping") of platelets by irreversibly binding to P2Y12 receptors.<unk>  inhibits platelet aggregation more rapidly, more consistently, and to a greater extent than clopidogrel The TRITON-TIMI 38 study compared<unk>  with clopidogrel, and showed that<unk>  reduced rates of ischaemic events, but increased bleeding risk. Overall mortality rates were similar for each drug. Clopidogrel, unlike<unk> , was issued a black box warning from the FDA on March 12, 2010, as the estimated 2–14% of the US population who have low levels of the CYP2C19 liver enzyme needed to activate clopidogrel may not get the full effect. Tests are available to predict if a patient would be susceptible to this problem or not. Unlike clopidogrel,<unk>  is effective in most individual with the exception in patients over the age of 75, weight under 60 kg, and patients with a history of stroke or TIA due to increased risk of bleeding, although several cases have been reported of decreased responsiveness to<unk> . It has been suggested that the decreased responsiveness observed in<unk>  is likely due to its low but significant frequency of High Platelet Reactivity (HPR). Pharmacodynamics<unk>  produces inhibition of platelet aggregation to 20 μM or 5 μM ADP, as measured by light transmission aggregometry. Following a 60-mg loading dose of the drug, about 90% of patients had at least 50% inhibition of platelet aggregation by one hour. Maximum platelet inhibition was about 80%. Mean steady-state inhibition of platelet aggregation was about 70% following three to five days of dosing at 10 mg daily after a 60-mg loading dose. Platelet aggregation gradually returns to baseline values over five to 9 days after discontinuation of<unk> , this time course being a reflection of new platelet production rather than pharmacokinetics of<unk> . Discontinuing clopidogrel 75 mg and initiating<unk>  10 mg with the next dose resulted in increased inhibition of platelet aggregation, but not greater than that typically produced by a 10-mg maintenance dose of<unk>  alone. Increasing platelet inhibition could increase bleeding risk. The relationship between inhibition of platelet aggregation and clinical activity has not been established. Pharmacokinetics The reaction of<unk>  (top left) to its active metabolite (R-138727, top right). The two structures at the bottom represent the inactive thiolactone; they are tautomers of each other.<unk>  is a prodrug and is rapidly metabolized by carboxylesterase 2 in the intestine and carboxylesterase 1 in the liver to a likewise inactive thiolactone, which is then converted by CYP3A4 and CYP2B6, and to a minor extent by CYP2C9 and CYP2C19, to a pharmacologically active metabolite (R-138727). R-138727 has an elimination half-life of about 7 hours (range 2 h to 15 h). Healthy subjects, patients with stable atherosclerosis, and patients undergoing PCI show similar pharmacokinetics.
Prasugrel
Ticagrelor
Elinogrel
Cetrorelix
Alteplase
Defibrotide
Oprelvekin
Eptifibatide