title: No inhibition of cytochrome P450 activities in human liver microsomes by sulpiride, an antipsychotic drug.
abstract: The effects of sulpiride, an antipsychotic drug, on cytochrome P450 (CYP) activities in human liver microsomes were investigated. Sulpiride at 50 or 500 microM concentration neither inhibited nor stimulated CYP1A2-mediated 7-ethoxyresorufin O-deethylation, CYP2C9-mediated tolbutamide hydroxylation, CYP2C19-mediated S-mephenytoin 4'-hydroxylation, CYP2D6-mediated debrisoquine 4-hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, CYP3A4-mediated nifedipine oxidation, or CYP3A4-mediated testosterone 6beta-hydroxylation. The free fractions of sulpiride in the incubation mixture estimated by ultracentrifugation were more than 90.5%. These results suggest that sulpiride would not cause clinically significant interactions with other drugs, which are metabolized by CYPs, via the inhibition of metabolism.
authors.affiliation: Post-marketing Development Research Center, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. toshiro_niwa@po.fujisawa.co.jp
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niwa
authors.forename: Sachiko
authors.initials: S
authors.lastname: Inoue
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Shiraga
authors.forename: Akira
authors.initials: A
authors.lastname: Takagi
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D013469:Sulpiride / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D013469:Sulpiride; D003577:Cytochrome P-450 Enzyme System