{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:31:00Z","timestamp":1773923460422,"version":"3.50.1"},"reference-count":28,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Insect microsomes expressing the 37 recombinant CYP2C9 variants were incubated in a 37\u00a0\u00b0C 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>CYP2C9<\/jats:italic>\n                      alleles when prescribing agomelatine in clinical practice. This study can provide valuable insights for personalized medicine and reduce adverse reactions to some extent.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.20973","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T08:37:01Z","timestamp":1773909421000},"page":"e20973","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Cytochrome P450 2C9 genetic polymorphism on agomelatine metabolism\n                    <i>in vitro<\/i>"],"prefix":"10.7717","volume":"14","author":[{"given":"Ping","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine,  Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhuan","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wenzhou Medical University, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taoye","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine,  Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wenzhou Medical University, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinwu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Wenzhou Seventh People\u2019s Hospital, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wenzhou Medical University, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dapeng","family":"Dai","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoxin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wenzhou Medical University, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianchang","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wenzhou Medical University, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Cai","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Beijing, 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