ArticlePeerJ2026
Effect of Cytochrome P450 2C9 genetic polymorphism on agomelatine metabolism
Article in PeerJ, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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11 authors.
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Abstract
Background: Genetic polymorphisms of CYP2C9 significantly influence the efficacy and safety of some drugs, which potentially lead to adverse effects and therapeutic failure. The aim of this study was to investigate the genetic polymorphism of 37 CYP2C9 alleles and evaluate their catalytic activities in agomelatine metabolism Methods: Insect microsomes expressing the 37 recombinant CYP2C9 variants were incubated in a 37 °C water bath with agomelatine. The main active metabolites of agomelatine were detected using a UPLC-MS/MS system. Then, the enzyme kinetic parameters of the 36 variants were calculated and compared with those of the wild-type CYP2C9*1. Results: 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
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