The effect of CYP2C19 genotype on the time course of platelet aggregation inhibition after clopidogrel administration

We evaluated the effect of CYP2C19 genotype over time on the antiplatelet response of clopidogrel in healthy subjects. Seventy subjects enrolled for a pharmacodynamic study and 22 subjects for a pharmacokinetic and pharmacodynamic study took 300 mg clopidogrel on the first day and 75 mg once daily f...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2014-08, Vol.54 (8), p.850-857
Main Authors: Kim, Ho-Sook, Cho, Doo-Yeoun, Park, Bo-Min, Bae, Soo-Kyoung, Yoon, Yune-Jung, Oh, Minkyung, Ghim, Jong-lyul, Kim, Eun-Young, Kim, Dong-Hyun, Shin, Jae-Gook
Format: Article
Language:English
Subjects:
Adult
Area Under Curve
Asian Continental Ancestry Group - genetics
clopidogrel
CYP2C19 genotype
Cytochrome P-450 CYP2C19 - genetics
Cytochrome P-450 CYP2C19 - metabolism
Genotype
Humans
Male
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - blood
Platelet Aggregation Inhibitors - pharmacokinetics
Platelet Aggregation Inhibitors - pharmacology
Polymorphism, Single Nucleotide
Sulfhydryl Compounds - blood
Ticlopidine - analogs & derivatives
Ticlopidine - blood
Ticlopidine - pharmacokinetics
Ticlopidine - pharmacology
time course of platelet aggregation inhibition
Young Adult
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Summary:We evaluated the effect of CYP2C19 genotype over time on the antiplatelet response of clopidogrel in healthy subjects. Seventy subjects enrolled for a pharmacodynamic study and 22 subjects for a pharmacokinetic and pharmacodynamic study took 300 mg clopidogrel on the first day and 75 mg once daily for six consecutive days. The subjects with CYP2C19 poor metabolizers (PM, N = 22) and intermediate metabolizers (IM, N = 37) had significantly delayed time to inhibition of platelet aggregation (IPA) compared with CYP2C19 extensive metabolizers (EM, N = 33) (12 vs. 9 vs. 2 hours as median Tmax, P  .05 for time effect; P 
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.225