| セッション情報 | The 4th International ForumI Drug-associated GI Injury：Advances of the pathogenesis and recent clinical topics 2. Recent clinical topics（a）Antiplatelet therapy：Mucosal injuries and drug interaction with PPI |
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| タイトル | IFI-2a-4：Role of CYP2C19 in antiplatelet therapy and PPIs |
| 演者 | Furuta Takahisa（Center for Clinical Research, Hamamatsu University, Japan） |
| 共同演者 | |
| 抄録 | Anti-platelet therapy is now widely performed in cardiovascular disorders. Aspirin and clopidogrel are the most important cornerstone agents in this therapy. Aspirin sometimes induces gastric mucosal injuries. Antiplatelet functions of aspirin and clopidogrel facilitate the bleeding from gastric lesions. Clopidogrel is metabolized to form an active metabolite. The main enzyme of active metabolization of clopidogrel is CYP2C19, which is polymorphic. In individuals with intermediate or poor metabolizer genotypes of CYP2C19, anti-platelet function of clopidogrel is decreased, resulting in the higher incidences of cardiovascular events. For the prevention of gastricduodenal bleeding during anti-platelet therapy, a concomitant use of a proton pump inhibitor（PPI）is recommended. Because PPIs are metabolized by CYP2C19, plasma levels and acid inhibitory functions of PPIs depend on CYP2C19 genotypes. In volunteers study, the prophylaxis effect of PPI for the dual treatment with aspirin and clopidogrel is decreased in rapid metabolizers of CYP2C19. Because clopidogrel and PPIs are metabolized by CYP2C19, drug-drug interaction occurs when these drugs are dosed concomitantly. Plasma levels of PPIs are increased and those of active metabolites of clopidogrel are decreased. Antiplatelet function of clopidogrel in attenuated by a PPI, even at low doses. This interaction cannot be avoided when clopidogrel and a PPI are doses separately. Several retrospective reports have demonstrated that a PPI increases incidences of cardiovascular events in patients taking clopidogrel. However, prospective studies cannot show that the clinical effect of clopidogrel is impaired by a PPI. On the contrary, incidences of gastroduodenal events during clopidogrel therapy are reportedly higher in the group without a PPI. Although there is a drug-drug interaction between two drugs, it has been thought that this interaction may not influence the clinical efficacy of clopidogrel, but that considering the risk of gastric bleeding, a PPI should be used especially in patients with a risk of gastroduodenal bleeding under well understanding of the interaction. The problems in this matter are as follows. Firstly, clopidogrel as well as aspirin is used without monitoring the platelet functions. Secondly, although it has been shown that genotypes of CYP2C19 influence effects of PPIs and clopidogrel in many papers, the testing of CYP2C19 polymorphism has not been covered by health insurance and can not be performed routinely. Individualized treatment based on pharmacogenomics and pharmacodynamics is strongly desired. |
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