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KMID : 0981820110310020091
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Korean Journal of Laboratory Medicine
2011 Volume.31 No. 2 p.91 ~ p.94
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Clinical, Pharmacokinetic, and Pharmacogenetic Determinants of Clopidogrel Resistance in Korean Patients with Acute Coronary Syndrome
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Park Kyoung-Jin
Chung Hae-Sun
Kim Suk-Ran
Kim Hee-Jin
Han Ju-Yong
Lee Soo-Youn
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Abstract
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Background: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS.
Methods: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed.
Results: A wide inter-individual variability was observed in platelet inhibition (0?76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients’ history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value<0.0001).
Conclusions: The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirm-ed that the genetic polymorphism of CYP2C19 could be importan
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KEYWORD
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Acute coronary syndrome, Clopidogrel resistance, CYP2C19, Korean, Platelet inhibition
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