Comparison of the Effects of Omeprazole and Rabeprazole on Ticlopidine Metabolism In Vitro
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概要
- 論文の詳細を見る
The thienopyridine derivative ticlopidine (TCL) is an inhibitor of adenosine diphosphate-induced platelet aggregation. Combination therapy with a thienopyridine derivative and aspirin is standard after coronary stenting, although more hemorrhagic complications occur with the combination therapy than with aspirin alone. A proton pump inhibitor (PPI) is required for prevention or treatment of upper gastrointestinal bleeding in such cases. We examined the effects of PPIs [omeprazole (OPZ) and rabeprazole (RPZ)] on TCL metabolism using pooled human liver microsomes prepared from various human liver blocks and 12 individual human liver microsomes. We calculated the Ki values of each PPI for TCL metabolic activity and compared the inhibitory effect of each PPI on TCL metabolism. The Ki values of OPZ and RPZ were 1.4 and 12.7 μM, respectively. The inhibitory effect of OPZ (78.6 ± 0.05%) was significantly greater than that of RPZ (24.2 ± 0.05%) (P < 0.001). Interestingly, a negative correlation existed between the inhibitory effect of OPZ and CYP2C19 activity (r = −0.909, P < 0.001). These results suggest that the inhibitory effect of OPZ is more potent than that of RPZ in vitro. In conclusion, RPZ appears preferable when administering TCL, aspirin, and a PPI in combination.
著者
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TAKEBA Yuko
Department of Pharmacology, St. Marianna University School of Medicine
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SUZUKI Satoshi
Research Institute of Angiocardiology and Cardiovascular Clinic,Faculty of Medicine,Kyushu Universit
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Matsumoto Naoki
Department Of Cardiology St. Marianna University School Of Medicine
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Itoh Fumio
Department Of Gastroenterology And Hepatology St. Marianna Medical University School Of Medicine
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Kobayashi Shinichi
Department Of Pharmacology School Of Medicine Showa University:shionogi Research Laboratories Shiono
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Watanabe M
The Institute Of Environmental Toxicology
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Kumai Toshio
Department Of Pharmacology St Marianna University School Of Medicine
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Kinoshita Yuichi
Department of Pharmacology, St. Marianna University School of Medicine, Japan
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Watanabe Minoru
Department Of Molecular And Cellular Pharmacology Nagoya City University
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Watanabe Minoru
Dep. Of Pharmacology St. Marianna Univ. School Of Medicine
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Kinoshita Yuichi
Dep. Of Pharmacology St. Marianna Univ. School Of Medicine
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Yoshida Yutoku
Department of Pharmacogenomics, St. Marianna University Graduate School of Medicine, Japan
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Ohba Keiichiro
Department of Pharmacogenomics, St. Marianna University Graduate School of Medicine, Japan
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Kobayashi Shinichi
Department Of Biomedical Engineering Graduate School Of Medicine University Of Tokyo
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Watanabe Minoru
Department Of Chemical Pharmacolgy Faculty Of Pharmaceutical Sciences Nagoya City University
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Kinoshita Yuichi
Department Of Pharmacology St. Marianna University School Of Medicine
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Takeba Yuko
Department Of Pharmacology St. Marianna University School Of Medicine
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Ohba Keiichiro
Department Of Pharmacogenomics St. Marianna University Graduate School Of Medicine
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Yoshida Yutoku
Department Of Pharmacogenomics St. Marianna University Graduate School Of Medicine
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