Non-antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different CYP2C19 genotype.

Abstract

Clopidogrel has been shown to improve endothelial function in vitro and in patients with coronary artery disease. However, it remains unclear whether such an effect of clopidogrel is associated with CYP2C19 polymorphisms that determine the antiplatelet effect of clopidogrel. After genotyping, 12 healthy participants were enrolled in the study. Among them, six participants were CYP2C19*1/*1 (extensive metabolizers; EM) and the other six participants were CYP2C19*2/*2 or *3 (poor metabolizers; PM). All participants received 300 mg clopidogel orally. Endothelial function was assessed by measurement of flow-mediated dilation of the brachial artery, and adenosine diphosphate-induced platelet aggregation was determined by using optical aggregometry at 0, 4 and 24 h after administration of 300 mg clopidogrel. Flow-mediated dilation was significantly higher at 4 and 24 h after a loading-dose administration of clopidogrel in both the CYP2C19 EM and PM groups, but showed no significant difference between the two groups. Adenosine diphosphate-induced platelet aggregation was significantly inhibited at 4 and 24 h after administration of clopidogrel in the CYP2C19 EM group. However, there was no statistical correlation between the change in flow-mediated dilation and adenosine diphosphate-induced platelet aggregation in the two CYP2C19 groups. This is the first study to report that clopidogrel improves endothelial function in healthy Chinese subjects, which is unrelated with the CYP2C19 genotype and independent of antiplatelet action.

• Authors: Yin-Zhuang Zhang, Bi-Lian Chen, Wei Zhang, Xin Cao
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 42 Issue 1 Pg. 22-6 (Jan 2015) ISSN: 1440-1681 [Electronic] Australia
• PMID: 25311974 (Publication Type: Journal Article)
• Copyright: © 2014 Wiley Publishing Asia Pty Ltd.

Chemical References

• Platelet Aggregation Inhibitors
• Clopidogrel
• CYP2C19 protein, human
• Cytochrome P-450 CYP2C19
• Ticlopidine

Topics

• Adult
• Asian People (genetics)
• Clopidogrel
• Cytochrome P-450 CYP2C19 (genetics)
• Endothelium, Vascular (drug effects, physiology)
• Genotype
• Humans
• Male
• Platelet Aggregation (drug effects, genetics)
• Platelet Aggregation Inhibitors (pharmacology)
• Ticlopidine (analogs & derivatives, pharmacology)
• Treatment Outcome
• Young Adult