Prediction of clopidogrel low responders by a rapid CYP2C19 activity test

Junichi Tazaki, Toshikazu Jinnai, Tomohisa Tada, Yoshihiro Kato, Takeru Makiyama, Tomoyuki Ikeda, Keiichiro Yamane, Yumiko Naruse, Kanako Takahashi, Haruyo Watanabe, Takeshi Kimura, Hisanori Horiuchi

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Aim: Clopidogrel, an essential drug for the prevention of stent thrombosis, is a prodrug activated by CYP enzyme family including CYP2C19. It is known that activity-defective polymorphisms of CYP2C19 (CYP2C19*2 and *3) are associated with reduced clopidogrel efficacy and poor prognosis. Recently, the 13 C-pantoprazole breath test is developed to evaluate the CYP2C19 activity. The aim of this study is to evaluated the efficiency of the CYP2C19 activity test as a predictor of antiplatelet effect of clopidogrel Methods: The CYP2C19 activity and the antiplatelet effect of clopidogrel were evaluated in 27 healthy volunteers. Change of the carbon isotope ratios ( 13CO 2/ 12CO 2) in expiration gas between before and after 13C-pantoprazole intake was evaluated as delta over baseline (DOB) ratio (‰). Results: DOB at 30 min was significantly lower in poor metabolizers (PMs) than extensive metabolizers (EM s) and intermediate metabolizers (IM s) (EM vs. PM, p = 0.0108; IM vs. PM, p = 0.016). The antiplatelet effect of clopidogrel was significantly different in three groups (inhibition of platelet aggregation: p = 0.0148, P2Y 12 reaction unit: p = 0.0241). DOB at 30 min was correlated with the antiplatelet effect of clopidogrel. A cut-off value of DOB at 30 min below 1.0‰ predicted PMs with 96% specificity and 100% sensitivity. Conclusions: The 13C-pantoprazole breath test can detect CYP2C19 PMs and predict low responders to clopidogrel rapidly.

Original languageEnglish
Pages (from-to)186-193
Number of pages8
JournalJournal of atherosclerosis and thrombosis
Volume19
Issue number2
DOIs
Publication statusPublished - 2012

Keywords

  • Antiplatelet therapy
  • CYP2C19 polymorphism
  • Clopidogrel

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

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