Beyond efficacy: pharmacokinetic differences between clopidogrel, prasugrel and ticagrelor.
BACKGROUND
Clinical nonresponse to clopidogrel has been associated with variability in response. This has led to the development of other P2Y12 receptor inhibitors, such as prasugrel and ticagrelor, with different pharmacokinetic characteristics that influence their pharmacodynamics.


METHODS
Clopidogrel response variability is attributable to its complex pharmacokinetics and is vulnerable to genetic polymorphisms in genes involved in absorption, metabolism and drug-drug interactions (i.e., proton pump inhibitors). Prasugrel which has a simpler metabolism, leading to greater bioavailability, seems to be less affected by genetic or drug-drug interactions and achieves a greater antiplatelet effect. Ticagrelor is the most novel compound approved with a simpler metabolism. Both prasugrel and ticagrelor reached their antiplatelet effect faster and to a much greater extent than clopidogrel. All these differences observed in kinetics explain, to some degree, the efficacy and safety profile observed in clinical trials for these molecules associated with other antiplatelet agents (aspirin, gpIIb/IIIa inhibitors) and anticoagulants.


CONCLUSIONS
Clopidogrel is still the best standard of care. However, the pharmacokinetic advantages of both prasugrel and ticagrelor allow clinicians to center patient management by selecting the best drug for the appropriate subject.
Department of Cardiology and Cardiovascular Surgery, Instituto FLENI, Montañes, Buenos Aires, Argentina. marianoagiorgi@hotmail.com
Mariano A
MA
Giorgi
Hernán
H
Cohen Arazi
Claudio D
CD
Gonzalez
Guillermo
G
Di Girolamo
D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077144:Clopidogrel; D006801:Humans; D010879:Piperazines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D059039:Standard of Care; D013876:Thiophenes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine