No inhibition of cytochrome P450 activities in human liver microsomes by sulpiride, an antipsychotic drug.
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.
Niwa
Toshiro
T
Post-marketing Development Research Center, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. toshiro_niwa@po.fujisawa.co.jp
Inoue
Sachiko
S
Shiraga
Toshifumi
T
Takagi
Akira
A
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*
D014150:Antipsychotic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D013469:Sulpiride; D003577:Cytochrome P-450 Enzyme System