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Recent developments in clopidogrel pharmacology and their relation to clinical outcomes.

Publication ,  Journal Article
Gurbel, PA; Antonino, MJ; Tantry, US
Published in: Expert Opin Drug Metab Toxicol
August 2009

Oral antiplatelet therapy with clopidogrel and aspirin is an important and widely prescribed strategy to prevent ischemic events in patients with cardiovascular diseases. However, the occurrence of thrombotic events including stent thrombosis is still high (> 10%). Current practice guidelines are mainly based on large-scale trials focusing on clinical endpoints and 'one size fits all' strategies of treating all patients with the same clopidogrel doses. Pharmacodynamic studies have demonstrated that the latter strategy is associated with wide response variability where a substantial percentage of patients show nonresponsivenes. Translational research studies have established the relation between clopidogrel nonresponsivenes or high on-treatment platelet reactivity to adverse clinical events, thereby establishing clopidogrel nonresponsivenes as an important emerging clinical entity. Clopidogrel response variability is primarily a pharmacokinetic phenomenon associated with insufficient active metabolite generation that is secondary to i) limited intestinal absorption affected by an ABCB1 gene polymorphism; ii) functional variability in P450 isoenzyme activity; and iii) a genetic polymorphism of CYP450 isoenzymes. Personalized antiplatelet treatment with higher clopidogrel doses in selected patients or with newer more potent P2Y(12) receptor blockers based on individual platelet function measurement can overcome some of the limitations of current clopidogrel treatment.

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Published In

Expert Opin Drug Metab Toxicol

DOI

EISSN

1744-7607

Publication Date

August 2009

Volume

5

Issue

8

Start / End Page

989 / 1004

Location

England

Related Subject Headings

  • Treatment Outcome
  • Ticlopidine
  • Receptors, Purinergic P2Y12
  • Purinergic P2 Receptor Antagonists
  • Polymorphism, Genetic
  • Platelet Aggregation Inhibitors
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Humans
  • Cytochrome P-450 Enzyme System
 

Citation

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Gurbel, P. A., Antonino, M. J., & Tantry, U. S. (2009). Recent developments in clopidogrel pharmacology and their relation to clinical outcomes. Expert Opin Drug Metab Toxicol, 5(8), 989–1004. https://doi.org/10.1517/17425250903107772
Gurbel, Paul A., Mark J. Antonino, and Udaya S. Tantry. “Recent developments in clopidogrel pharmacology and their relation to clinical outcomes.Expert Opin Drug Metab Toxicol 5, no. 8 (August 2009): 989–1004. https://doi.org/10.1517/17425250903107772.
Gurbel PA, Antonino MJ, Tantry US. Recent developments in clopidogrel pharmacology and their relation to clinical outcomes. Expert Opin Drug Metab Toxicol. 2009 Aug;5(8):989–1004.
Gurbel, Paul A., et al. “Recent developments in clopidogrel pharmacology and their relation to clinical outcomes.Expert Opin Drug Metab Toxicol, vol. 5, no. 8, Aug. 2009, pp. 989–1004. Pubmed, doi:10.1517/17425250903107772.
Gurbel PA, Antonino MJ, Tantry US. Recent developments in clopidogrel pharmacology and their relation to clinical outcomes. Expert Opin Drug Metab Toxicol. 2009 Aug;5(8):989–1004.

Published In

Expert Opin Drug Metab Toxicol

DOI

EISSN

1744-7607

Publication Date

August 2009

Volume

5

Issue

8

Start / End Page

989 / 1004

Location

England

Related Subject Headings

  • Treatment Outcome
  • Ticlopidine
  • Receptors, Purinergic P2Y12
  • Purinergic P2 Receptor Antagonists
  • Polymorphism, Genetic
  • Platelet Aggregation Inhibitors
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Humans
  • Cytochrome P-450 Enzyme System