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Single-dose pharmacodynamics of clopidogrel
J J Thebault1, G Kieffer, R Cariou
1Institut Aster, Hôpital Cognacq-Jay, Paris, France.
Seminars in Thrombosis and Hemostasis
|August 10, 1999
Summary
Clopidogrel, a novel P2Y12 inhibitor, effectively inhibits ADP-induced platelet aggregation in a dose-dependent manner up to 400 mg. This study informed the selection of clopidogrel
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Hematology
Background:
- Clopidogrel is a novel P2Y12 receptor antagonist.
- Platelet aggregation plays a crucial role in thrombotic events.
Purpose of the Study:
- To evaluate the dose-response relationship and efficacy of clopidogrel in inhibiting platelet aggregation.
- To assess the effect of clopidogrel on bleeding time.
Main Methods:
- Two single-dose studies in healthy male volunteers.
- Randomized, double-blind, placebo-controlled and crossover designs were employed.
- Platelet aggregation induced by ADP and collagen was measured, along with bleeding time.
Main Results:
- Clopidogrel significantly inhibited ADP-induced platelet aggregation in a dose-dependent manner up to 400 mg.
- Inhibition of platelet aggregation remained stable for up to 72 hours post-400 mg dose.
- A slight-to-moderate inhibitory effect on collagen-induced aggregation and a statistically significant prolongation of bleeding time at higher doses were observed.
Conclusions:
- Clopidogrel demonstrates potent and sustained inhibition of ADP-mediated platelet aggregation.
- The findings support the use of clopidogrel as an antiplatelet agent and informed the selection of its loading dose.