Comparison of the Effects of Omeprazole and Rabeprazole on Ticlopidine Metabolism In Vitro

Journal of Pharmacological Sciences

Satoshi Suzuki¹  Toshio Kumai³  Yuko Takeba²  Minoru Watanabe²  Yutoku Yoshida³  Naoki Matsumoto²  Yuichi Kinoshita²  Fumio Itoh⁴  Keiichiro Ohba³  Shinichi Kobayashi² 

[1]Research Laboratories, HAB Research Organization, Japan

[2]Department of Pharmacology, St. Marianna University School of Medicine, Japan

[3]Department of Pharmacogenomics, St. Marianna University Graduate School of Medicine, Japan

[4]Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Japan

关键词: ticlopidine;    proton-pump inhibitor;    drug–drug interaction;    clopidogrel;    cytochrome P450 (CYP) 2C19;   

DOI  :  10.1254/jphs.11048FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(29)Cited-By(3)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.

【 授权许可】

Unknown