Effect of Cytochrome P450 2C9 genetic polymorphism on agomelatine metabolism <i>in vitro</i>

Relative to CYP2C9*1, four variants exhibited no significant difference in enzyme activity. Eleven variants exhibited significantly higher intrinsic clearance values, while 13 variants exhibited significantly reduced intrinsic clearance values. The remaining eight variants demonstrated complex metabolic patterns; these variants do not produce the two metabolites equally, and they inhibited the appearance of one metabolite but promoted the production of another metabolite. These results suggest that special attention should be given to subjects carrying poor metabolizers of <i>CYP2C9</i> alleles when prescribing agomelatine in clinical practice. This study can provide valuable insights for personalized medicine and reduce adverse reactions to some extent.