Pharmacokinetics and pharmacodynamics of oral P2Y12 inhibitors during the acute phase of a myocardial infarction: A systematic review.
BACKGROUND
The immediate administration of oral antiplatelet therapy in the form of aspirin plus a P2Y12 inhibitor is the universally recognised standard of care for patients who present with acute myocardial infarction. Despite strong recommendations for their use, there are a paucity of data describing their onset of action and clinical efficacy during the short time frames from confirmation of diagnosis to reperfusion with primary percutaneous coronary intervention.


OBJECTIVE
To complete a systematic review evaluating the currently available evidence regarding the pharmacokinetic and pharmacodynamic activity of orally administered clopidogrel, prasugrel and ticagrelor during the acute phase of a myocardial infarction in relation to mechanical reperfusion with primary percutaneous coronary angioplasty.


METHODS
We searched PubMed and EMBASE databases up to January 2016 using the terms outlined in our search strategy.


RESULTS
Twelve papers were included in our final analysis; seven relating to pharmacodynamic studies, one to a pharmacokinetic study and four to pharmacokinetic/pharmacodynamic studies.


CONCLUSIONS
Our results indicate that despite the administration of oral P2Y12 inhibitors including newer more potent agents that should allow for greater and more consistent levels of platelet inhibition, the physiological state of ST segment elevation MI (STEMI) and the co-administration of opioid based analgesia are associated with a reduction in the degree of platelet inhibition achieved following their administration.
Department of Cardiology, The Heart and Lung Centre, The Royal Wolverhampton Hospitals NHS Trust, WV10 0QP, UK; Department of Pharmacy, The Royal Wolverhampton Hospitals NHS Trust, WV10 0QP, UK.
Nazish
N
Khan
School of Pharmacy, College of Medical and Dental Sciences, University of Birmingham, B15 2TH, UK.
Anthony R
AR
Cox
Department of Cardiology, The Heart and Lung Centre, The Royal Wolverhampton Hospitals NHS Trust, WV10 0QP, UK. Electronic address: jamescotton@nhs.net.
James M
JM
Cotton
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000077144:Clopidogrel; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000601:surgery; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
Aspirin; Clopidogrel; Inhibition of platelet activity (IPA); P2Y12 inhibitors; Platelet function assays; Prasugrel; Primary percutaneous coronary intervention; ST elevation myocardial infarction; STEMI; Ticagrelor