title: Comparison of the effects of omeprazole and rabeprazole on ticlopidine metabolism in vitro.
abstract: 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 K(i) values of each PPI for TCL metabolic activity and compared the inhibitory effect of each PPI on TCL metabolism. The K(i) 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.
authors.affiliation: Department of Pharmacology, St. Marianna University School of Medicine, Japan. y2kinoshita@marianna-u.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeba
authors.forename: Yutoku
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Ohba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Fumio
authors.initials: F
authors.lastname: Itoh
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumai
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000897:Anti-Ulcer Agents; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D009853:Omeprazole / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors; D064750:Rabeprazole; D013988:Ticlopidine / Q000378:metabolism*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D010975:Platelet Aggregation Inhibitors; D064750:Rabeprazole; D009853:Omeprazole; D013988:Ticlopidine