Clopidogrel Pharmacogenetics Bench to Bedside - A Practical Application
Clopidogrel is a prodrug with high inter-individual response variability. Clopidogrel is
converted to an active drug through an enzyme encoded by the gene named CYP2C19.
Individuals with genetically-impaired CYP2C19 metabolism have lower capacity to convert the
prodrug to its active form. Consequently, these individuals have lower blood levels of the
activated form of clopidogrel, diminished antiplatelet responses, and higher rates of
cardiovascular events and stent thrombosis. Increasing doses of clopidogrel in such
patients represents a possible approach to managing the gene-drug interaction.
The purpose of this study is to evaluate whether increasing the dose of clopidogrel
increases antiplatelet responses and active metabolite exposure in individuals with
genetically reduced CYP2C19 metabolism relative to those with normal CYP2C19 metabolism.
The primary objective is to assess changes in clopidogrel response and exposure at three
clopidogrel dose levels and with coadministration of omeprazole.
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in platelet aggregation following therapy with Clopidogrel
platelet aggregation will be measured at baseline and at 4-hours post-dose of clopidogrel on day 1 and at 4-hours post-dose of clopidogrel on day 8. The primary endpoint of this study will be the change in maximal platelet aggregation 4-hours post-dose (MPA4; units are a percentage) on day 8 of each study period compared to baseline.
Baseline, Day 1, Day 8
Richard B Horenstein, M.D.
University of Maryland
United States: Institutional Review Board
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