[Thienopyridines in the treatment and prevention of cardiovascular diseases. Part II. Clinical pharmacology of clopidogrel].
In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the second communication we describe in detail clinical pharmacokinetics and pharmacodynamics of the most often used thienopyridine derivative - clopidogrel. We discuss results of randomized studies and clinical observations which have shown that pharmacokinetics of clopidogrel might vary substantially in dependence of polymorphisms of genes responsible for synthesis of P2Y12 receptors of platelets or cytochromic isoenzymes P-450 CYP of liver with participation of which formation of active metabolite of clopidogrel occurs. Contrary to practically healthy people in patients with various forms of ischemic heart disease (IHD) concomitant therapy, for instance some statins and calcium antagonists, can affect clopidogrel pharmacokinetics. Pharmacodynamics of clopidogrel in patients with IHD with acute coronary syndrome or diabetes mellitus or before percutaneous coronary interventions (PCI) also differs from that in healthy people, because in these patients hyperaggregation of platelets takes place initially and antiaggregatory action of clopidogrel is less expressed. In 10-30% of patients with IHD partial or complete resistance to antiaggregation action of clopidogrel is detected, which according to some observations is combined with elevated risk of thrombotic cardiac complications after PCI. Possible causes of resistance to clopidogrel and ways of its overcoming are discussed.
D V
DV
Preobrazhenskiĭ
B A
BA
Sidorenko
T A
TA
Batyraliev
A
A
Vural
M
M
Islek
O
O
Avsar
D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D000077144:Clopidogrel; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C446540:thienopyridine; D000077144:Clopidogrel; D013988:Ticlopidine