{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:42Z","timestamp":1790621922759,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Aim<\/jats:title>\n \n Ischaemic stroke is a global health issue, and\n clopidogrel<\/jats:ext-link>\n is widely used for secondary prevention and undergoes hepatic activation by cytochrome 2C19 (\n CYP2C19<\/jats:italic>\n ) into its active thiol metabolite (H4\u2010clopi). Although genetic polymorphisms are key determinants of this process, inflammatory states, such as acute ischaemic stroke, may cause phenotype\u2013genotype mismatch (phenoconversion) and temporarily reduce\n CYP2C19<\/jats:italic>\n enzyme activity.\n <\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n \n This pharmacokinetic study was performed in Iranian patients with mild acute ischaemic stroke (NIHSS\u2009\u2264\u20095) who were prescribed clopidogrel for 21\u2009days. Genotyping was conducted by real\u2010time PCR.\n CYP2C19<\/jats:italic>\n activity and Clopidogrel metabolism were assessed in both the acute and post\u2010acute phase (21\u2009days after acute ischaemic stroke) by using the\n omeprazole<\/jats:ext-link>\n metabolic ratio (MR) and the maximum plasma concentration (Cmax) of H4\u2010clopi, respectively. Laboratory parameters and demographic characteristics were also recorded.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Thirty\u2010three patients were enrolled (mean age 63\u2009\u00b1\u00a010.5\u00a0years; 66% male). Genotype results were consistent with previous reports in ethnically matched healthy populations.\n CYP2C19<\/jats:italic>\n activity was significantly reduced in the acute phase and recovered only partially in the post\u2010acute phase. Regardless of genotype, H4\u2010clopi Cmax was significantly lower in ischaemic stroke patients than in healthy controls in both phases, with no significant interphase improvement (\n p<\/jats:italic>\n \u00a0<\u20090.05). Inflammatory markers and NIHSS scores significantly decreased in the post\u2010acute phase (\n p<\/jats:italic>\n \u00a0<\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings demonstrate that genotyping alone may be insufficient to identify poor metabolizers, highlighting the importance of direct measurement of\n CYP2C19<\/jats:italic>\n activity and consideration of alternative antiplatelet approaches.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/bcp.70635","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:00:31Z","timestamp":1780581631000},"page":"3424-3436","source":"Crossref","is-referenced-by-count":0,"title":["Impaired clopidogrel activation due to\n CYP2C19<\/i>\n phenoconversion after mild acute ischaemic stroke"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4857-3599","authenticated-orcid":false,"given":"Maryam","family":"Alaei","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy Tehran University of Medical Sciences Tehran Iran"},{"name":"Research Center for Rational Use of Drugs (RCRUD) Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hooshyar","family":"Honarmand","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadreza","family":"Gheini","sequence":"additional","affiliation":[{"name":"Neurology ward, Sina Hospital, School of Medicine Tehran University of Medical Sciences Tehran 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