title: Metabolic differences of current thienopyridine antiplatelet agents.
abstract: BACKGROUND
  Antithrombotics are one of the most commonly prescribed classes of medication around the world. The thienopyridines are an integral part of antithrombotic therapy and are prescribed for various indications including acute coronary syndrome, peripheral vascular disease and cerebrovascular disease. These drugs have distinct metabolic pathways, which lead to the formation of active metabolites that produce both observed clinical differences as well as pharmacokinetic and pharmacodynamic differences in response.
  
  
  METHODS
  The authors describe the pharmacokinetic and pharmacodynamic behavior of three of the currently available thienopyridines, namely ticlopidine, clopidogrel and prasugrel. The authors also describe and discuss the drug interaction and pharmacogenomic factors which may impact safety and drug efficacy.
  
  
  CONCLUSIONS
  P2Y(12)-ADP receptor antagonism has proven to be effective at preventing thrombosis. Differences in the activation of these drugs, cytochrome metabolism, concomitant drug use and pharmacogenomics have an impact on thienopyridine use. Clopidogrel remains the thienopyridine drug with the most approved indications for use. Prasugrel has proven to be efficacious but is associated with a higher bleeding risk in comparison to clopidogrel and therefore has to be used in appropriate clinical indications.
authors.affiliation: Loyola University Chicago, Department of Pathology and Pharmacology, 2160 S. First Avenue, Maywood, Illinois 60153, USA. jfareed@lumc.edu
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
authors.forename: Walter
authors.initials: W
authors.lastname: Jeske
authors.forename: Indermohan
authors.initials: I
authors.lastname: Thethi
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics*; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D008658:Inactivation, Metabolic; D010597:Pharmacogenetics; D010879:Piperazines / Q000493:pharmacokinetics*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000493:pharmacokinetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D005343:Fibrinolytic Agents; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D011725:Pyridines; D013876:Thiophenes; C446540:thienopyridine; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine